doi.org/10.26434/chemrxiv.12752312.v1

Congener-Specific Partition Properties of Chlorinated ParaffinsEvaluated with COSMOtherm and Gas Chromatographic RetentionIndicesJort Hammer, Hidenori Matsukami, Satoshi Endo

Submitted date: 03/08/2020 • Posted date: 04/08/2020Licence: CC BY-NC-ND 4.0Citation information: Hammer, Jort; Matsukami, Hidenori; Endo, Satoshi (2020): Congener-Specific PartitionProperties of Chlorinated Paraffins Evaluated with COSMOtherm and Gas Chromatographic RetentionIndices. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12752312.v1

Chlorinated Paraffins (CPs) are high volume production chemicals and have been found in various organismsincluding humans and in environmental samples from remote regions. It is thus of great importance tounderstand the physical-chemical properties of CPs. In this study, gas chromatographic (GC) retentionindexes (RIs) of 26 CP congeners were measured on various polar and nonpolar columns to investigate therelationships between the molecular structure and the partition properties. Retention measurements show thatanalytical standards of individual CPs often contain several stereoisomers. RI values show that chlorinationpattern have a large influence on the polarity of CPs. Single Cl substitutions (-CHCl-, -CH2Cl) generallyincrease polarity of CPs. However, many consecutive -CHCl- units (e.g., 1,2,3,4,5,6-C11Cl6) increase polarityless than expected from the total number of -CHCl- units. Polyparameter linear free energy relationshipdescriptors show that polarity difference between CP congeners can be explained by the H-bond donatingproperties of CPs. RI values of CP congeners were predicted using the quantum chemically based predictiontool COSMOthermX. Predicted RI values correlate well with the experimental data (R2, 0.975–0.995),indicating that COSMOthermX can be used to accurately predict the retention of CP congeners on GCcolumns.

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Congener-specific partition properties of chlorinated paraffins

evaluated with COSMOtherm and gas chromatographic retention

indices

Jort Hammer*, Hidenori Matsukami, Satoshi Endo

National Institute for Environmental Studies (NIES), Center for Health and Environmental Risk

Research, Onogawa 16-2, 305-8506 Tsukuba, Ibaraki, Japan

*Corresponding author

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AbstractChlorinated Paraffins (CPs) are high volume production chemicals and have been found

in various organisms including humans and in environmental samples from remote regions. It is

thus of great importance to understand the physical-chemical properties of CPs. In this study,

gas chromatographic (GC) retention indexes (RIs) of 26 CP congeners were measured on various

polar and nonpolar columns to investigate the relationships between the molecular structure

and the partition properties. Retention measurements show that analytical standards of

individual CPs often contain several stereoisomers. RI values show that chlorination pattern

have a large influence on the polarity of CPs. Single Cl substitutions (-CHCl-, -CH 2Cl) generally

increase polarity of CPs. However, many consecutive -CHCl- units (e.g., 1,2,3,4,5,6-C 11Cl6)

increase polarity less than expected from the total number of -CHCl- units. Polyparameter linear

free energy relationship descriptors show that polarity difference between CP congeners can be

explained by the H-bond donating properties of CPs. RI values of CP congeners were predicted

using the quantum chemically based prediction tool COSMOthermX. Predicted RI values

correlate well with the experimental data (R2, 0.975–0.995), indicating that COSMOthermX can

be used to accurately predict the retention of CP congeners on GC columns.

IntroductionChlorinated Paraffins (CPs) are a group of substances that are applied in various products

as plasticizers, coolants and flame retardants because of their chemical and thermal stability.1

CPs are high-volume production chemicals (>1 million metric tonnes yr-1) and are regularly

released into the environment during production, transportation, and recycling processes and

through leaching and volatilization from landfills.2–4 Short-chain chlorinated paraffins (SCCPs;

C10-C13) are found to be persistent, bioaccumulative and toxic (PBT) to aquatic organisms. In

2017, SCCPs were classified as persistent organic pollutants (POPs) under the Stockholm

Convention and subsequently the production of SCCPs has stopped in the US, Japan, Canada

and Europe, and will soon be restricted in China.5,6 Since the PBT properties of medium-chain

(MCCPs: C14-C17) and long-chain (LCCPs; C18 and longer) chlorinated paraffins are less studied and

a matter of debate, they are currently still being produced and used as alternatives for SCCPs.7

Therefore, the overall world-wide production of CPs still upholds its increasing trend from the

1950s, albeit with a recent shift from SCCPs towards MCCPs and LCCPs.

CP molecules are usually produced by free-radical chlorination of n-alkanes. This

chlorination reaction shows low positional selectivity and produces many congeners and

isomers and does not discriminate between stereoisomers.8 CP mixtures can therefore comprise

thousands of congeners with differing chain lengths and chlorination patterns. Currently, due to

the complexity of CP mixtures and the lack of analytical standards, no analytical methods are

available for the identification of individual congeners in CP mixtures or any samples

contaminated with CPs.9 The large variability in molecular structure suggests that intermolecular

interaction properties also vary substantially. Intermolecular interactions determine the

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partitioning behavior of CPs and need to be understood to describe the environmental fate,

bioaccumulation, and toxicity of CPs. The broad bands of CP signals observed in

chromatographic analysis do suggest that congeners have a range of partition properties.10

The objective of this work is to describe the relationship between structure and

molecular interaction properties of CPs through experimental and quantum chemically based

approaches. Gas chromatography (GC) was used to experimentally investigate the molecular

interaction properties, as the retention time of the analyte on a GC column is directly related to

the molecular interactions between the column coating and the analyte molecule. Different GC

column coatings were selected with a range of polarity to elucidate the polar interaction

properties of CPs. The physico-chemical properties of CP congeners were evaluated by deriving

poly-parameter linear free energy relationship (ppLFER) descriptors from the measured data.

Lastly, retention times were predicted using a quantum chemically based tool, COSMOthermX

(COSMOlogic GmbH & Co. KG). COSMOthermX has previously been used to predict partition

coefficients such as octanol-water partition coefficients for CPs.11,12 Because COSMOthermX

requires only the molecular structure as input parameter, it could be a useful tool to predict the

retention and, more generally, partition properties of CP congeners with diverse structures.

MethodsChemicals

Analytical standards of 2,5,6,9-C10Cl4, 1,2,5,6,9,10-C10Cl6 and 2,3,4,5,6,7,8,9-C10Cl8 were

provided by Dr. Ehrenstorfer GmbH (Augsburg, Germany). Standards of 1,1,1,3-C10Cl4, 1,1,1,3-

C11Cl4, 1,1,1,3-C12Cl4, 1,1,1,3-C13Cl4, 1,1,1,3-C14Cl4, 1,1,1,3,9,10-C10Cl6, 1,1,1,3,10,11-C11Cl6,

1,1,1,3,11,12-C12Cl6, 1,1,1,3,12,13-C13Cl6, 1,1,1,3,8,10,10,10-C10Cl8, 1,1,1,3,9,11,11,11-C11Cl8,

1,1,1,3,10,12,12,12-C12Cl8, 1,1,1,3,11,13,13,13-C13Cl8, 1,1,1,3,12,14,14,14-C14Cl8, 1,2,9,10-C10Cl4,

1,2,10,11-C11Cl4, 1,2,13,14-C14Cl4, 1,2,3,4,5,6-C11Cl6, 4,5,7,8-C11Cl4, 2,3,4,5-C10Cl4 and 2,3,4,5-C12Cl4

were obtained from Chiron AS (Trondheim, Norway). 1,5,5,6,6,10-C10Cl6, which was

commercially available from Cambridge Isotope Laboratories Inc. (Tewksbury, MA, USA), was

donated by Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). C16, C18, C20-n-alcohols, a mixture of

C7-40-n-alkanes and a mixture of C4, C6, C8, C10, C12, C14, C16, C18, C20, C22, C24-methyl esters (FAMEs)

were obtained from Sigma-Aldrich Japan (Tokyo, Japan). C8, C10, C12-n-alcohols were obtained

from Tokyo Chemical Industry (Tokyo, Japan). A mixture of polycyclic aromatic hydrocarbons

(PAHs) containing naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene,

anthracene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene,

benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, indeno[1,2,3-cd]pyrene and

benzo[ghi]perylene was obtained from Sigma-Aldrich Japan (Tokyo, Japan). Specifics on purities

and concentrations of the CP analytical standards can be found in Supplementary Table S1.

Columns

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Six GC columns were used for the retention measurements in this study (Table 1). The

GC columns were selected to cover a wide range of polarity based on polarity scales provided by

manufacturers. The SPB-Octyl column is of nonpolar nature and the least polar column in this

study. Its coating consists of poly(50% n-octyl/50% methylsiloxane) and exerts retention mainly

via van der Waals interactions. The polar property of columns HP-5ms, InertCap-17ms and DB-

17ms originates from the presence of phenyl groups in the dimethylsiloxane (HP-5ms and

InertCap-17ms) or silarylene-siloxane polymer (DB-17ms) structure of the column coating.

These columns contain 5% or 50% phenyl groups. Phenyl groups have π electrons that have

weak hydrogen (H)-bond accepting properties. The DB-225ms column, with a coating of 50%

cyanopropylphenyl/50% dimethylsiloxane-equivalent silarylene-siloxane copolymer, contains a

polar nitrile group that acts as a H-bond acceptor. The polar property of the SolGel-WAX column

originates from the ether oxygen atoms in poly(ethylene glycol), which has strong H-bond

accepting properties. All columns had the dimension of 30 m 0.25 mm 0.25 μm.

Retention measurements

A program with linear oven temperature increase was applied on all columns until the

recommended maximum temperature was reached (240-300°C). Helium was used as carrier gas

and a flow rate of 1.2 mL/min was maintained throughout all measurements. Retention

measurements for SPB-Octyl, DB-17ms, DB-225ms, and SolGel-WAX were performed using cool

on-column injections on an Agilent 7890 GC, followed by atmospheric pressure chemical

ionization (APCI) and mass selective detection (Agilent 6530 QTOF-MS) (See Supplementary

Section S2 for the optimization of APCI-QTOF-MS parameters for CPs). An injection volume of 2

μL was used. The on-column injector temperature was kept at the initial oven temperature (60

or 70°C) for 0.1 min and increased with 100°C/min to the maximum oven temperature. The

oven temperature was kept at 60 or 70°C for 0.1 min and increased with 10°C/min to the

maximum temperature shown in Table 1. More details are stated in the Supplementary Section

S2. Retention measurements of SPB-Octyl and SolGel-WAX were also performed on a different

system (7890A/7000A triple quadrupole GC/MS, Agilent Technologies) and HP-5ms and

InertCap-17ms only on this system because of its better availability in our laboratory. On the

triple quadrupole GC/MS system, splitless injection at 250°C and electron ionization (EI) were

used. Peak patterns were similar on both systems, and the retention indices (RIs; see below for

the definition) differed only by 7 on average and 20 in the worst case. In contrast to the EI-MS

detector, the APCI-QTOF-MS method allows for a detection of pseudo-molecular ions and thus

better identification of peaks that belong to the stated CP isomers. Therefore, if the

measurements were done on both systems, data from APCI-QTOF-MS were considered for the

latter discussions. Peak identifications for the EI-MS chromatograms of HP-5ms and InertCap-

17ms were performed by using the APCI-TOF-MS chromatograms of SPB-Octyl and DB-17ms,

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respectively, as reference, because the peak patterns were highly similar (see the results

section).

Table 1. Polymer coating compositions of the GC columns and structures of the surrogate

molecules used in COSMOthermX. The circled parts (red) on the molecular fragments refer to

the groups that were disregarded using the weight string function in COSMOthermX. GC system

Column Coating composition

according to

manufacturer

Manufacturer GC oven

temperature

program

GC system /

Detection

Fragments representing the polymer phase in

COSMOthermX

SPB-Octyl poly(50% n-octy/

50% dimethylsiloxane)Supelco

70 °C (1 min)

10 °C/min

280 °C (10 min)

Agilent 7890 GC /

Agilent 6530 QTOF-

MS

HP-5mspoly(5% diphenyl/

95% dimethylsiloxane)

Agilent

Technologies

70 °C (0.1 min)

10 °C/min

280 °C (10 min)

Agilent 7890A GC/

Agilent 7000A

Triple Quad GC/MS

DB-17mspoly(50% phenyl/

50% dimethylsiloxane)1

Agilent

Technologies

60 °C (1 min)

10 °C/min

300 °C (10 min)

Agilent 7890 GC /

Agilent 6530 QTOF-

MS

InertCap-17mspoly(50% diphenyl/

50% dimethylsiloxane) GL Sciences

70 °C (1 min) 20

°C/min

300 °C (10 min)

Agilent 7890A GC /

Agilent 7000A

Triple Quad GC/MS

DB-225ms

poly(50% cyano-

propylphenyl/ 50%

dimethylsiloxane) 1

Agilent

Technologies

70 °C (0.1 min)

10 °C/min

240 °C (15 min)

Agilent 7890 GC /

Agilent 6530 QTOF-

MS

SolGel-WAX Polyethylene glycolSGE Analytical

Science

70 °C (1 min)

10 °C/min

280 °C (5 min)

Agilent 7890 GC /

Agilent 6530 QTOF-

MS

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1 Silarylene-siloxane copolymer; 2 Instead of 5 and 95% mole fractions, 5.3 and 94.7% was used as the liquid phase composition

for HP-5ms in COSMOthermX since the larger fragment contains not only diphenylsiloxane, but dimethylsiloxane as well.

RIs of CPs, n-alcohols, n-alkylmethyl esters, PAHs and n-alkanes were obtained using the

linear temperature-programmed retention index system (LTPRI). This system is used to establish

retention indices for retention times measured under a program with linear temperature

increase:13,14

1)

where Rti is the retention time of the analyte, Rtx is the retention time of the n-alkane eluting

directly before Rti, Rtx+1 is the retention time of the n-alkane eluting directly after Rti and RIx is

the retention index of the n-alkane that corresponds to Rtx. The retention indices of n-alkanes

are defined as its number of carbon atoms times a hundred.

ppLFER descriptors

ppLFERs are useful in characterizing interaction properties that determine partitioning

behavior of chemicals. ppLFERs are multiple linear regression models that use several solute

descriptors as independent variables for the calculation of partition coefficients.15 The most

frequently used ppLFER for the gas-condensed phase partitioning, established by Abraham et

al,16 has the general form:

log K = c + eE + sS + aA + bB + lL 2)

where log K is the logarithmic partition coefficient. The uppercase letters on the right-hand side

of the equation are the solute descriptors: E, excess molar refraction; S, dipolarity/polarizability

parameter; A, H-bond donating property; B, H-bond accepting property and L, logarithmic

hexadecane-air partition coefficient. The lowercase letters are the system parameters. Each

term quantitatively describes the energetic contribution of a molecular interaction to log K.

Since none of the columns from the current study has H-bond donating properties, the bB term

can be ignored. Solute descriptors S and A are both responsible for the polar interactions of the

chemical: S is related to the surface electrostatic property and is thought to represent polar

interactions that result in part from the partial charge distribution over the molecular surface.17

A reflects more specific interactions resulting from H-bond donating sites of the solute

molecule. The L solute descriptor describes the non-specific van der Waals interactions and also

includes the energy needed for cavity formation.15,18 The eE term also describes the van der

Waals interactions but usually has only minor contributions to log K. For more detailed

explanations of the equation, we refer to refs 13-15.

RI=Rt i−Rt x

Rt x+1−Rt x

×100+RI x

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In this study, temperature-programmed RIs instead of log K are correlated with the

ppLFER descriptors. Because temperature-programmed RI is related but not directly

proportional to log K,19 the use of ppLFER for the RI is an approximation. For a more accurate

investigation, isothermal retention measurements would be better suited, although much more

time-consuming than temperature-programmed measurements, as isothermal measurements

must be performed at many temperatures to cover diverse CP structures. The purpose of using

ppLFERs in the current work is to compare semi-quantitatively the polar interaction properties

of CP congeners with varying structures and not to derive accurate solute descriptors that could

be used for later predictions.

Prediction of RI with COSMOthermX

COSMOthermX software is based on the COSMO-RS theory, which uses quantum

mechanics and statistical thermodynamics calculations to determine the chemical potential of a

solute in solution and can thereby predict partition coefficients. Gas-GC coating (i.e., air-

polymer) partition coefficients were predicted following the method by Goss (2011).20

Molecular structures of CPs, reference compounds and polymer coatings were expressed with

SMILES strings, which were then converted to SDF files. Quantum chemical calculations and

conformer selection were performed using COSMOconfX (version 4.3, COSMOlogic) with

TURBOMOL 7.3, which yield a complete set of relevant conformations with full geometry

optimization in the gas phase and in the conductor reference state. The gas phase energy and

COSMO files of the CPs and reference compounds were then used in the COSMOthermX

software (version 19.04; parameterization: BP_TZVPD_FINE_19) to calculate air-polymer

partition coefficients (Kair-polymer). To represent the molecular structure of polymer coating,

monomers or oligomers of the coating polymer structure provided by the manufacturer were

used. For the quantum chemical calculations performed by COSMOconfX, the end groups of

these monomer or oligomer were end-capped with CH3 groups. The CH3 groups were later

disregarded during COSMOthermX calculations by giving a weighting factor of 0, following the

approach by Goss (2011).20 All these surrogate structures used for coating polymers are shown

in Table 1. The polymer structure of the HP-5ms column consists of 5% diphenylsiloxane and

95% dimethylsiloxane and we represented this structure with a mixture of diphenylsiloxane and

dimethylsiloxane in the respective mole fractions (see Table 1) in the COSMOthermX

calculations. For the SolGel-WAX column, an end-capped trimer of ethylene glycol was used, as

in ref 17.

All calculations in COSMOthermX were performed with the combinatorial term switched

off, as is recommended for polymer by the COSMOthermX user guide.22,23 All conformers

generated by COSMOconfX of the target chemicals were used for the calculation of air-polymer

partition coefficients. However, to reduce calculation times, only the top 5 low-energy

conformers returned by COSMOconfX (_c0 to _c4 suffixes) were selected to represent the

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polymer phases. For some CPs, COSMOconfX returned conformers with R or S configurations

that were inconsistent with the input structure. This problem did not occur when we turned off

RDKit and only used Balloon for the generation initial conformers on the Windows version of

COSMOconfX.

For each chemical and coating phase, Kair-polymer was predicted at 5 temperature steps

between 373.15 and 573.15 K. Then, linear regression between log Kair-polymer and 1/T was

established, and a hypothetical eluting temperature was interpolated at a column-specific,

characteristic Kair-polymer value that is derived from experimental data. This eluting temperature

was considered analogous to the retention time and used to derive RI, following eq 2. A more

detailed explanation about how RI values were predicted from COSMOthermX calculations is

presented in the Supplementary Section S1.

Because the stereometric structure of the isomers present in the CP standards is

unknown, partition coefficients were calculated for all possible diastereomers using

COSMOthermX. A pair of enantiomers was represented by a single structure in the

COSMOthermX calculation, because partition coefficients of enantiomers are the same in

isotropic phases. The predictability of the COSMOthermX program was tested by comparing the

mean of predicted RIs for all possible diastereomers and the weighted mean of the measured RI

values of the CP standards from the GC system. RI values of PAHs were calculated but not used

in testing the predictability of COSMOthermX, as their predicted RI values were systematically

deviated from the measured values (see Supplementary Table S4).

Results and discussionDetermination of GC retention times and RI

Retention measurements showed the presence of multiple peaks in most of the CP

analytical standards. Generally, CP congeners with a high number of possible diastereomers

given their molecular structure showed multiple peaks with a substantial peak area of the same

(pseudo)molecular ion. For example, on the SPB-Octyl column, 10 peaks within a minute of

retention time were found for 1,2,3,4,5,6-C11Cl6, which has 10 possible diastereomers (a pair of

enantiomers are considered one structure). In contrast, 1,1,1,3,9,10-C10Cl6 (2 possible

diastereomers) only showed one peak (Supplementary Fig. S1A and S1B). For one standard,

2,5,6,9-C10Cl4 (6 possible diastereomers), the manufacturer-provided certificate of analysis

stated the presence of three diastereomers without details on the exact stereometric structure

(e.g., S and R notation). While we indeed observed three peaks on the nonpolar SPB-Octyl

column, 7 peaks were found on the most polar SolGel-WAX column (Fig. 1), showing increased

separation through polar interactions. As exceptional cases, 1,2,5,6,9,10-C10Cl6 (6 possible

diastereomers) only showed one peak on all columns (Supplementary Fig. S1C) and

2,3,4,5,6,7,8,9-C10Cl8 (72 possible diastereomers) showed 3 peaks on the SPB-Octyl column, and

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only 1 peak on the SolGel-WAX (Supplementary Fig. S1D). These standards likely contain a

limited number of diastereomers. Some CP standards with only few or no possible

diastereomers resulted in a higher number of peaks. For example, 1,1,1,3-C10Cl4 (no

diastereomer) showed 5 peaks over 3 minutes of retention time on the SPB-Octyl column

(Supplementary Fig. S1E) and 4 peaks over 5 minutes of retention time on the SolGel-WAX

column. Most of the peaks in these chromatograms were small and are likely constitutional

isomers (i.e., impurities).

Figure 1. The Chromatogram of 2,3,6,9-C10Cl4 measured on the SolGel-WAX column. The

manufacturer-provided certificate of analysis of this analytical standard stated the presence of

three diastereomers.

As a representative RI value for a CP congener with multiple peaks, the mean of the RI

values weighted by the peak areas was calculated and used in the following discussions. While

we are aware that peak areas do not always reflect the relative abundance of CP isomers

present,24 this approach deemed better than simply calculating the mean of RIs for all peaks

without weighting, particularly in cases where one or a few major peaks appear with many

small peaks.

We note that no retention times of 1,1,1,3,11,12-C12Cl6, 1,1,1,3,9,10,10,10-C10Cl8 and

1,5,5,6,6,10-C10Cl6 could be determined on the SolGel-WAX column, as their peaks were broad

and the response was low (Supplementary Fig. S1F). This peak broadening is probably because

of thermal degradation, as a high temperature (280°C) was needed to elute these congeners.

Indeed, 1,5,5,6,6,10-C10Cl6 and 1,1,1,3,9,10,10,10-C10Cl8 were detected on the other highly polar

column DB-225ms, for which a lower temperature (240°C) for elution was applied.

Comparison of RIs on polar and nonpolar columns

Since polar compounds are retained more by polar coatings, comparing RI values

between columns of different polarity allows for the characterization of the polar interaction

properties of CP molecules and substructures. RIs of CPs on polar columns were always higher

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than those on the nonpolar SPB-Octyl column, showing the significance of polar interaction

properties for all CP standards (Fig. 2). The range of RIs (or separation of

diastereomer/constitutional isomer peaks) for each CP standard was usually greater on polar

columns, meaning that the isomers are better separated with polar retention mechanisms

instead of van der Waals interactions only.

A series of CP congeners with -CH2- increments show that RI on all columns increased

with 102 to 119 per addition of -CH2- to the alkyl chain. These values are similar to the RI values

of n-alcohols (102–107 per methylene) and n-alkylmethyl esters (100–105 per methylene, see

Supplementary Fig. S2).

Chlorine substitution on the alkyl chain generally increased RI to an extent depending on

the column polarity and the position of Cl. For example, the RI of 1,2,9,10-C10Cl4 on the SPB-

Octyl column is greater by 229 than that of a constitutional isomer 1,1,1,3-C10Cl4. The retention

on the SPB-Octyl column is driven by van der Waals interactions, which are correlated to the

molecular surface area of the molecule.25 The four Cl atoms of 1,2,9,10-C10Cl4 are distributed

over the alkyl chain and increase the molecular surface area more than the four Cl atoms of

1,1,1,3-C10Cl4 that are shifted on one side.

Figure 2B shows ΔRI, defined as the RI of a column subtracted by the RI of SPB-Octyl to

clarify the contributions of polar interactions to the retention. Larger ΔRI values are observed

with increasing column polarity, while the trends of ΔRI over different congeners are similar for

all columns. Generally, a single Cl substitution on -CH2- to -CHCl- increases the polarity of CPs.

However, actual contributions appear to depend strongly on the neighboring structure of the

-CHCl- group. A vicinal substitution pattern (-CHCl-CHCl-) does not increase the polarity so much

as an isolated -CHCl-. This is clearly shown with 2,3,4,5,6,7,8,9-C10Cl8, which shows only an

intermediate ΔRI although having the highest number of -CHCl- units. In a vicinal substitution

pattern, the proximity of -CHCl- groups might interfere with, and lower, the polarity and/or H-

bond properties of a neighboring -CHCl- group. In contrast, a single Cl substitution on a terminal

carbon (-CH3) is less influenced by Cl on the neighboring carbon. Comparison of the 5

tetrachloro (Cl4) congeners is illustrative for these trends: 2,5,6,9-C10Cl4 (2 isolated Cl and a pair

of vicinal Cl) and 1,2,9,10-C10Cl4 (2 pairs of vicinal Cl at the ends) show the highest ΔRI, followed

by 4,5,7,8- C11Cl4 (2 pairs of vicinal Cl) and 2,3,4,5-C10Cl4 (4 consecutive, vicinal Cl). 1,1,1,3-C10Cl4

is the least polar of the measured CPs even though it contains one isolated -CHCl- group. This

shows that CCl3 has a much smaller contribution to polarity than 3 -CHCl-. It is interesting to

note that ΔRI of 1,1,1,3-C10Cl4 is about half that of 1,1,1,3,9,10,10,10-C10Cl8. As the latter has

double the CCl3-CH2-CHCl- substitution pattern, this observation suggests that the additivity

principle may hold for the polarity of CPs, provided that the two structural units are far enough

apart. The highest ΔRI was observed for 1,2,5,6,9,10-C10Cl6 (3 pairs of vicinal Cl, of which 2 pairs

at the ends). 1,5,5,6,6,10-C10Cl6 is the only CP standard with double chlorinated carbons and

shows the second highest ΔRI. Comparison to 1,2,5,6,9,10-C10Cl6 suggests that -CCl2-CCl2- may

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be less polar than 4 chlorines all as vicinal -CHCl- groups. Overall, the total number of -CHCl-

groups is not decisive for the polarity of CPs and the chlorination pattern needs to be

considered.

Figure 2. The measured RI on GC columns (A), the measured RIs subtracted by the measured RI

on the SPB-Octyl column (ΔRI) (B), and RI values predicted by COSMOthermX subtracted by

predicted RI values of the SPB-Octyl column (C) for a selection of CP standards. The compounds

are ordered according to the ΔRI for DB-225ms (polar column with data available for most CPs).

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The vertical error bars in panels A and B show the range of measured RIs for multiple peaks,

while the vertical error bars in panel C show the range of predicted RI values for CPs with

multiple diastereomers. Corrections were applied to predicted RIs (see text).

Describing polarity using ppLFERs

To investigate the types and the extent of polar interactions with CPs, ppLFER solute

descriptors were derived. The A and S descriptors describe the polarity of the CPs relevant for

GC retention times. First, the E values of CPs were obtained using the structure based

estimation method from the UFZ-LSER database,26 because E has been considered a simple

additive property.16 The E values obtained are presented in Supplementary Table S3a. Second, L

values were determined from SPB-Octyl data. The SPB-Octyl column exerts minimal polar

interactions, and system parameters s and a were therefore set to 0. Thus,

RI = c + eE + lL 3)

Here, the measured RI values and the solute descriptors (E, L) of n-alcohols, n-alkylmethyl

esters, n-alkanes and PAHs (Table 2b) were used to calibrate system parameters (c, e, l) for SPB-

Octyl by least-square multiple linear regression. The result is given in Supplementary Table S2.

The solute descriptors for these chemicals were obtained from the UFZ-LSER database.26 Then,

from the system parameters and E and RI values of CPs, L values were calculated

(Supplementary Table S3a):

L = (RI – c – eE)/l 4)

The A and S solute descriptors of CPs were calculated from the rest of the data. The

ppLFER model fit the calibration data well with R2 of 0.995-0.997 and the standard deviation

(SD) of 36-59. System parameters for all columns were qualitatively in good agreement with

those reported by Poole et al. using isothermal measurements (Supplementary Table S2). The a

and s system parameters are in the order of the expected polarity of the columns: SPB-Octyl <

HP-5ms << DB-17ms < InertCap-17ms << DB-225ms < SolGel-WAX. The ppLFER equations for the

columns were transformed into:

RI – c – eE – lL = sS + aA 5)

S and A were determined from multiple linear regression with 0 intercept. The results are given

in Supplementary Fig. S3. The standard errors of S and A were relatively high. This can be

because of the incompatible results for the two most polar columns, DB-225ms and SolGel-

WAX. As the e, a and s system parameters of the SolGel-WAX column are higher than those of

the DB-225ms column, one would expect that RIs on the SolGel-WAX column would also be

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higher for all CPs. However, as Fig. 2 shows, RIs for SolGel-WAX were just as much as or even

lower than those for DB-225ms. These conflicting results may cause a relatively large error in A

and S.

As an attempt, we obtained A and S with the RI data for all but the SolGel-WAX column

and for all but the DB-225ms column. While the resulting A and S descriptor values differ (on

average 0.40 and 0.16, respectively), the trend across CP congeners remains the same between

the two approaches (Fig. 3). The S descriptor generally increased with the number of

chlorinated carbons. The lowest values were found for 1,1,1,3-C10Cl4 and highest for

1,2,5,6,9,10-C10Cl6 and 2,3,4,5,6,7,8,9-C10Cl8 (Fig. 3 and Supplementary Table S2). The A solute

descriptor values were not related to the number of chlorines but rather to specific chlorination

patterns. Substructures -CH2Cl and -CHCl- tend to increase A, but with the striking exception

that compounds with consecutive -CHCl- structures (i.e., 2,3,4,5-C10Cl4 and 2,3,4,5,6,7,8,9-C10Cl8)

had lower A descriptor values compared to CPs with the same number but a more distributed

chlorination pattern (i.e., 4,5,7,8-C11Cl4, 2,5,6,9-C10Cl4 and 1,2,5,6,9,10-C10Cl6). The differences in

ΔRI between constitutional isomers observed in the previous section are thus more related to

H-bond donating properties (A) of the isomers.

The polar property of chlorinated carbon moieties stems from the high electronegativity

of the Cl atom compared to that of the C atom. In a -CHCl- structure, the relatively high electron

affinity of Cl has an inductive effect on C which results in a positive partial charge on the H

atom. This makes the -CHCl- structure polar (positive S) and the H atom is then prone to act as a

H-bond donor (positive A). Such an inductive effect of Cl and the resulting H-bond donor

property are well known for small chloroalkanes such as dichloromethane (A = 0.1) and

chloroform (A = 0.15). However, in CP structures with vicinal -CHCl-, the Cl atom is often in

proximity of the H atom of the neighboring -CHCl- structure which appear to diminish the ability

of the H to fully act as a H-bond donor. Having 4 or more consecutive -CHCl- structures put each

H atom in an even more crowded environment and brings back A to near 0 (Fig. 3). This

interpretation is consistent with the existing knowledge on A for hexachlorocyclohexane (HCH)

isomers. A values for α- and γ-HCHs are 0, whereas β-HCH poses a significant A value (0.12).27

Because of the different rotational configurations of the six -CHCl- units, β-HCH can take a

conformation that maximizes the exposition of H atoms to the surrounding, whereas α- and γ-

HCHs cannot do so.

A CCl3-CH2-CHCl- structure in 1,1,1,3-C10Cl4 has a minimal H-bonding property (see Fig.

3), which may be only attributable to the single -CHCl-. The -CCl3 group has no H-bond donor

site and does not appear to make the neighboring -CH2- acidic (similar case for 1,1,1-

trichloroethane with A = 0). However, a single Cl on the terminal carbon in a CH2Cl-CHCl-

structure adds to H-bond donating properties of the CP (see A of 1,1,1,3-C10Cl4 < 1,1,1,3,9,10-

C10Cl6). 1,2,3,4,5,6-Cl10Cl6 also contains this substructure although A is low, possibly due to steric

effects or interference from the neighboring consecutive CHCl structure.

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The inconsistent results for SolGel-WAX and DB-225ms can have several causes. For

example, n-alkanes might undergo interfacial adsorption and can be retained under a mixed-

mode retention mechanism on polar columns, which makes n-alkanes less suitable as reference

compounds for determining RI values.28 The exact reason is however difficult to conclude from

the current data.

Figure 3. Solute descriptors E, A, S and L for a selection of CPs. S and A descriptors were

determined using RI values from all columns while omitting either the SolGel-WAX or the DB-

225ms column. Doing so has no influence on the determined E and L descriptor values.

COSMOthermX predictions

The COSMOthermX-predicted RIs correlated well with the measured RIs of CPs with an

R2 between 0.975 and 0.995 (Supplementary Fig. S4). There is even high 1:1 agreement

between predicted and measured RIs for SPB-Octyl, HP-5ms, and SolGel-WAX (RMSE: 44-72).

The agreement, however, was lower for the columns DB-17ms, InertCap-17ms and DB-225ms

(RMSE: 222-280). The CP group shows a trend that is not parallel to n-alkanes for these three

columns (Supplementary Fig. S4), and thus the discrepancy increases with increasing RI value.

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The polymer coating of these columns contains a high proportion of phenyl groups (50% phenyl

or diphenyl groups) and, apparently, the interaction properties of these groups with the CP

structures is not fully captured by COSMOthermX. To make use of the high correlations between

predicted and measured RIs, we applied an empirical correction to the predicted RI values by

using the regression formula of predicted vs measured RI values for CPs (Supplementary Fig.

S5). The results are shown in Fig. 4 and Supplementary Fig. S5. The RSME values after correction

were between 21 and 75.

ΔRI values were calculated using the predicted RIs to test whether COSMOthermX can

capture differences in polarity between CP congeners (Fig. 2C). Comparing Fig. 2B and 2C

indicates that the overall trend agrees well with the experimentally observed ΔRIs. Thus,

COSMOthermX correctly reflects polarity differences between CPs with differing chlorination

patterns. The only discrepancy appears that COSMOthermX slightly overestimates the ΔRI

values of CPs with many consecutive -CHCl- groups (i.e., 1,2,3,4,5,6-C11Cl6 and 2,3,4,5,6,7,8,9-

C10Cl8). This statement however is conditional, because these two congeners have many possible

diastereomers (16 and 70, respectively), for which COSMOthermX calculated a relatively wide

range of ΔRIs. Currently, we do not know which diastereomers are present in the analytical

standards.

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Measured RI

Pre

dic

ted

RI

HP-5msDB-17msInertCap-17msDB-225ms

SPB-Octyl

SolGel-WAX

Figure 4. The RI values for CP congeners predicted by COSMOthermX for all columns in this

study against the measured RI values from the GC system. Empirical corrections were applied to

RI predictions (see text).

Effects of diastereomerism

The range of predicted RI values by COSMOthermX shown in Supplementary Fig. S4 and

S5 indicates the potential effects of diastereomerism of the CP on the partition properties (e.g.,

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2,3,4,5,6,7,8,9-C10Cl8). COSMOthermX predicts an increasing range of RI with increasing polarity

of the polymer phase, which was also observed in the retention measurements on the GC

systems. While CPs with many possible diastereomers usually showed a wide range in measured

RI values, predicted RI values often span over an even wider range, suggesting that not all

possible diastereomers are present in the CP standards. Comparing the two diastereomers of

2,3,4,5,6,7,8,9-C10Cl8, with the highest and lowest predicted RI values on the DB-225ms column

((2R,3S,4S,5S,6S,7S,8S,9R)-2,3,4,5,6,7,8,9-C10Cl8 and (2R,3R,4S,5S,6S,7S,8R,9R)-2,3,4,5,6,7,8,9-

C10Cl8, predicted RI of 2721 and 2304, respectively), we can see that a difference in rotational

configurations around the chiral carbons can result in distinctly different three-dimensional

shapes (Fig. 5). Overall, according to the results from COSMOthermX, the difference between

diastereomers can greatly affect the 3D-structure of the CP molecules, which, in turn, affects

the interaction properties of the molecule and its partition behavior.

Figure 5. The lowest-energy conformers (_c0 suffix) of (2R,3S,4S,5S,6S,7S,8S,9R)-2,3,4,5,6,7,8,9-

C10Cl8 (A) and (2R,3R,4S,5S,6S,7S,8R,9R)-2,3,4,5,6,7,8,9-C10Cl8 (B), generated by COSMOconfX.

Both are diastereomers of 2,3,4,5,6,7,8,9-C10Cl8.

ConclusionsInspection of RI values of CPs from GC columns with different polarity shows that the

chlorination pattern plays an important role in determining polar interactions of CPs. Isolated

-CHCl- groups or a pair of two vicinal -CHCl- are more polar than patterns with three or more

consecutive -CHCl- groups. Polarity is also increased when a single Cl atom is present at the

terminal carbon (e.g., -CH2Cl), whereas three Cl atoms at the terminal (-CCl3) add least to

polarity of the CP molecules.

Determining ppLFER descriptors for CPs shows that polarity differs significantly between

CP chlorination patterns and confirm the importance of Cl positioning to the H-bond donating

properties (A) of CPs. The calculated solute descriptors show that H-bond interactions are lower

for CPs with many consecutive -CHCl- groups than for CPs with a more distributed chlorination

pattern.

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Predictions from COSMOthermX show that the quantum chemically based modelling

approach is capable of predicting RI values and can reflect the effect of variations in chlorination

pattern on the interaction properties of CPs. This result supports the general accuracy of

COSMOthermX to predict partition coefficients of CPs. As future work, retention time

predictions by COSMOthermX for a diverse set of congeners could be compared to measured

chromatograms of CPs in environmental samples or in complex technical mixtures to infer the

congener compositions present.

Data availabilityThe authors declare that all data supporting the findings of this study are available

within the article and its supplementary information file.

References1. van Mourik, L. M., Gaus, C., Leonards, P. E. G. & de Boer, J. Chlorinated paraffins in the environment:

A review on their production, fate, levels and trends between 2010 and 2015. Chemosphere 155,

415–428 (2016).

2. Tomy, G. T., Fisk, A. T., Westmore, J. B. & Muir, D. C. G. Environmental chemistry and toxicology of

polychlorinated n-alkanes. Rev. Environ. Contam. Toxicol. 158, 53–128 (1998).

3. Sverko, E., Tomy, G. T., Märvin, C. H. & Muir, D. C. G. Improving the quality of environmental

measurements on short chain chlorinated paraffins to support global regulatory efforts. Environ. Sci.

Technol. 46, 4697–4698 (2012).

4. Brandsma, S. H. et al. Chlorinated Paraffins in Car Tires Recycled to Rubber Granulates and

Playground Tiles. Environ. Sci. Technol. 53, 7595–7603 (2019).

5. Vorkamp, K., Balmer, J., Hung, H., Letcher, R. J. & Rigét, F. F. A review of chlorinated paraffin

contamination in Arctic ecosystems. Emerg. Contam. 5, 219–231 (2019).

6. ChemicalWatch. China updates severely restricted toxic chemicals catalogue. 1

https://chemicalwatch.com/87564/china-updates-severely-restricted-toxic-chemicals-catalogue

(2020).

7. Brandsma, S. H. et al. Medium-Chain Chlorinated Paraffins (CPs) Dominate in Australian Sewage

Sludge. Environ. Sci. Technol. 51, 3364–3372 (2017).

8. Nikiforov, V. A. Synthesis of Polychloroalkanes. in Chlorinated Paraffins (ed. de Boer, J.) 41–82 (2010).

doi:10.1007/698_2009_40.

9. van Mourik, L. M. et al. The underlying challenges that arise when analysing short-chain chlorinated

paraffins in environmental matrices. J. Chromatogr. A 1610, 460550 (2020).

10. Yuan, B. et al. Accumulation of Short-, Medium-, and Long-Chain Chlorinated Paraffins in Marine and

Terrestrial Animals from Scandinavia. Environ. Sci. Technol. 53, 3526–3537 (2019).

11. Glüge, J., Bogdal, C., Scheringer, M., Buser, A. M. & Hungerbühler, K. Calculation of Physicochemical

Properties for Short- and Medium-Chain Chlorinated Paraffins. J. Phys. Chem. Ref. Data 42, 023103

(2013).

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12. Endo, S. & Hammer, J. Predicting Partition Coefficients of Short-Chain Chlorinated Paraffin Congeners

by Combining COSMO-RS and Fragment Contribution Model Approaches. Preprint (2020)

doi:10.26434/chemrxiv.12525656.

13. Martos, P. a., Saraullo, A. & Pawliszyn, J. Estimation of Air/Coating Distribution Coefficients for Solid

Phase Microextraction Using Retention Indexes from Linear Temperature-Programmed Capillary Gas

Chromatography. Application to the Sampling and Analysis of Total Petroleum Hydrocarbons in Air.

Anal. Chem. 69, 402–408 (1997).

14. van Den Dool, H. & Dec. Kratz, P. A generalization of the retention index system including linear

temperature programmed gas-liquid partition chromatography. J. Chromatogr. A 11, 463–471

(1963).

15. Endo, S. & Goss, K. U. Applications of polyparameter linear free energy relationships in

environmental chemistry. Environ. Sci. Technol. 48, 12477–12491 (2014).

16. Abraham, M. H., Ibrahim, A. & Zissimos, A. M. Determination of sets of solute descriptors from

chromatographic measurements. J. Chromatogr. A 1037, 29–47 (2004).

17. Arey, J. S., Green, W. H. & Gschwend, P. M. The Electrostatic Origin of Abraham’s Solute Polarity

Parameter. J. Phys. Chem. B 109, 7564–7573 (2005).

18. Poole, C. F. & Poole, S. K. Separation characteristics of wall-coated open-tubular columns for gas

chromatography. J. Chromatogr. A 1184, 254–280 (2008).

19. Curvers, J., Rijks, J., Cramers, C., Knauss, K. & Larson, P. Temperature programmed retention indices:

Calculation from isothermal data. Part 1: Theory. J. High Resolut. Chromatogr. 8, 607–610 (1985).

20. Goss, K.-U. Predicting Equilibrium Sorption of Neutral Organic Chemicals into Various Polymeric

Sorbents with COSMO-RS. Anal. Chem. 83, 5304–5308 (2011).

21. COSMOlogic GmbH. COSMO-RS. (COSMOlogic, 2015).

22. COSMOlogic GmbH & Co. KG. COSMOthermX User Guide. (2016).

23. Goss, K.-U. Predicting Equilibrium Sorption of Neutral Organic Chemicals into Various Polymeric

Sorbents with COSMO-RS. Anal. Chem. 83, 5304–5308 (2011).

24. Schinkel, L. et al. Deconvolution of Mass Spectral Interferences of Chlorinated Alkanes and Their

Thermal Degradation Products: Chlorinated Alkenes. Anal. Chem. 89, 5923–5931 (2017).

25. van Noort, P. C. M., Haftka, J. J. H. & Parsons, J. R. A simple McGowan specific volume correction for

branching in hydrocarbons and its consequences for some other solvation parameter values.

Chemosphere 84, 1102–1107 (2011).

26. Ulrich, N. ; Endo, S. ;. Brown, T. N. ;. Watanabe, N. ;. Bronner, G. ;. Abraham, M. H. ;. Goss, K. U. UFZ-

LSER database v 3.2 [Internet]. Available from http://www.ufz.de/lserd (2017).

27. Goss, K.-U., Arp, H. P. H., Bronner, G. & Niederer, C. Partition Behavior of Hexachlorocyclohexane

Isomers. J. Chem. Eng. Data 53, 750–754 (2008).

28. González, F. R., Castells, R. C. & Nardillo, A. M. Behavior of n-alkanes on poly(oxyethylene) capillary

columns: Evaluation of interfacial effects. J. Chromatogr. A 927, 111–120 (2001).

Author informationCorresponding author

Jort Hammer

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Hammer.jort@nies.go.jp

ORCID: 0000-0002-1403-2631

Additional informationThe authors declare no competing financial interest.

Supplementary information is available for this paper at...

Author contributionsStudy design: JH, SE. GC-MS measurements: JH, HM. COSMO-RS calculations: JH. Data

evaluation: JH, SE. Drafting of manuscript: JH. Revising of manuscript: JH, SE, HM.

AcknowledgementsThis research was supported by the Environment Research and Technology Development

Fund SII-3-1 (JPMEERF18S20300) of the Environmental Restoration and Conservation Agency,

Japan. COSMOconfX and TURBOMOL calculations were performed with the NIES supercomputer

system. We thank Kai-Uwe Goss for their valuable comments on the manuscript, and Yoshinori

Fujimine (Otsuka Pharmaceutical Co., Ltd.) for donating the standard solution of 1,5,5,6,6,10-

C10Cl6.

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download fileview on ChemRxiv20200803-CPs_GC-COSMO_Hammer-Endo.docx (919.36 KiB)

Congener-specific partition properties of chlorinated paraffins 1

evaluated with COSMOtherm and gas chromatographic retention 2

indices 3

4

Jort Hammer*, Hidenori Matsukami, Satoshi Endo 5

6

National Institute for Environmental Studies (NIES), Center for Health and Environmental Risk 7

Research, Onogawa 16-2, 305-8506 Tsukuba, Ibaraki, Japan 8

9

*Corresponding author 10

Abstract 11

Chlorinated Paraffins (CPs) are high volume production chemicals and have been found 12

in various organisms including humans and in environmental samples from remote regions. It is 13

thus of great importance to understand the physical-chemical properties of CPs. In this study, gas 14

chromatographic (GC) retention indexes (RIs) of 26 CP congeners were measured on various polar 15

and nonpolar columns to investigate the relationships between the molecular structure and the 16

partition properties. Retention measurements show that analytical standards of individual CPs 17

often contain several stereoisomers. RI values show that chlorination pattern have a large 18

influence on the polarity of CPs. Single Cl substitutions (-CHCl-, -CH2Cl) generally increase polarity 19

of CPs. However, many consecutive -CHCl- units (e.g., 1,2,3,4,5,6-C11Cl6) increase polarity less 20

than expected from the total number of -CHCl- units. Polyparameter linear free energy 21

relationship descriptors show that polarity difference between CP congeners can be explained 22

by the H-bond donating properties of CPs. RI values of CP congeners were predicted using the 23

quantum chemically based prediction tool COSMOthermX. Predicted RI values correlate well with 24

the experimental data (R2, 0.975–0.995), indicating that COSMOthermX can be used to accurately 25

predict the retention of CP congeners on GC columns. 26

27

Introduction 28

Chlorinated Paraffins (CPs) are a group of substances that are applied in various products 29

as plasticizers, coolants and flame retardants because of their chemical and thermal stability.1 30

CPs are high-volume production chemicals (>1 million metric tonnes yr-1) and are regularly 31

released into the environment during production, transportation, and recycling processes and 32

through leaching and volatilization from landfills.2–4 Short-chain chlorinated paraffins (SCCPs; C10-33

C13) are found to be persistent, bioaccumulative and toxic (PBT) to aquatic organisms. In 2017, 34

SCCPs were classified as persistent organic pollutants (POPs) under the Stockholm Convention 35

and subsequently the production of SCCPs has stopped in the US, Japan, Canada and Europe, and 36

will soon be restricted in China.5,6 Since the PBT properties of medium-chain (MCCPs: C14-C17) and 37

long-chain (LCCPs; C18 and longer) chlorinated paraffins are less studied and a matter of debate, 38

they are currently still being produced and used as alternatives for SCCPs.7 Therefore, the overall 39

world-wide production of CPs still upholds its increasing trend from the 1950s, albeit with a 40

recent shift from SCCPs towards MCCPs and LCCPs. 41

CP molecules are usually produced by free-radical chlorination of n-alkanes. This 42

chlorination reaction shows low positional selectivity and produces many congeners and isomers 43

and does not discriminate between stereoisomers.8 CP mixtures can therefore comprise 44

thousands of congeners with differing chain lengths and chlorination patterns. Currently, due to 45

the complexity of CP mixtures and the lack of analytical standards, no analytical methods are 46

available for the identification of individual congeners in CP mixtures or any samples 47

contaminated with CPs.9 The large variability in molecular structure suggests that intermolecular 48

interaction properties also vary substantially. Intermolecular interactions determine the 49

partitioning behavior of CPs and need to be understood to describe the environmental fate, 50

bioaccumulation, and toxicity of CPs. The broad bands of CP signals observed in chromatographic 51

analysis do suggest that congeners have a range of partition properties.10 52

The objective of this work is to describe the relationship between structure and molecular 53

interaction properties of CPs through experimental and quantum chemically based approaches. 54

Gas chromatography (GC) was used to experimentally investigate the molecular interaction 55

properties, as the retention time of the analyte on a GC column is directly related to the 56

molecular interactions between the column coating and the analyte molecule. Different GC 57

column coatings were selected with a range of polarity to elucidate the polar interaction 58

properties of CPs. The physico-chemical properties of CP congeners were evaluated by deriving 59

poly-parameter linear free energy relationship (ppLFER) descriptors from the measured data. 60

Lastly, retention times were predicted using a quantum chemically based tool, COSMOthermX 61

(COSMOlogic GmbH & Co. KG). COSMOthermX has previously been used to predict partition 62

coefficients such as octanol-water partition coefficients for CPs.11,12 Because COSMOthermX 63

requires only the molecular structure as input parameter, it could be a useful tool to predict the 64

retention and, more generally, partition properties of CP congeners with diverse structures. 65

66

Methods 67

Chemicals 68

Analytical standards of 2,5,6,9-C10Cl4, 1,2,5,6,9,10-C10Cl6 and 2,3,4,5,6,7,8,9-C10Cl8 were 69

provided by Dr. Ehrenstorfer GmbH (Augsburg, Germany). Standards of 1,1,1,3-C10Cl4, 1,1,1,3-70

C11Cl4, 1,1,1,3-C12Cl4, 1,1,1,3-C13Cl4, 1,1,1,3-C14Cl4, 1,1,1,3,9,10-C10Cl6, 1,1,1,3,10,11-C11Cl6, 71

1,1,1,3,11,12-C12Cl6, 1,1,1,3,12,13-C13Cl6, 1,1,1,3,8,10,10,10-C10Cl8, 1,1,1,3,9,11,11,11-C11Cl8, 72

1,1,1,3,10,12,12,12-C12Cl8, 1,1,1,3,11,13,13,13-C13Cl8, 1,1,1,3,12,14,14,14-C14Cl8, 1,2,9,10-73

C10Cl4, 1,2,10,11-C11Cl4, 1,2,13,14-C14Cl4, 1,2,3,4,5,6-C11Cl6, 4,5,7,8-C11Cl4, 2,3,4,5-C10Cl4 and 74

2,3,4,5-C12Cl4 were obtained from Chiron AS (Trondheim, Norway). 1,5,5,6,6,10-C10Cl6, which 75

was commercially available from Cambridge Isotope Laboratories Inc. (Tewksbury, MA, USA), 76

was donated by Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). C16, C18, C20-n-alcohols, a 77

mixture of C7-40-n-alkanes and a mixture of C4, C6, C8, C10, C12, C14, C16, C18, C20, C22, C24-methyl 78

esters (FAMEs) were obtained from Sigma-Aldrich Japan (Tokyo, Japan). C8, C10, C12-n-alcohols 79

were obtained from Tokyo Chemical Industry (Tokyo, Japan). A mixture of polycyclic aromatic 80

hydrocarbons (PAHs) containing naphthalene, acenaphthylene, acenaphthene, fluorene, 81

phenanthrene, anthracene, fluoranthene, pyrene, benz[a]anthracene, chrysene, 82

benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, 83

indeno[1,2,3-cd]pyrene and benzo[ghi]perylene was obtained from Sigma-Aldrich Japan (Tokyo, 84

Japan). Specifics on purities and concentrations of the CP analytical standards can be found in 85

Supplementary Table S1. 86

87

Columns 88

Six GC columns were used for the retention measurements in this study (Table 1). The GC 89

columns were selected to cover a wide range of polarity based on polarity scales provided by 90

manufacturers. The SPB-Octyl column is of nonpolar nature and the least polar column in this 91

study. Its coating consists of poly(50% n-octyl/50% methylsiloxane) and exerts retention mainly 92

via van der Waals interactions. The polar property of columns HP-5ms, InertCap-17ms and DB-93

17ms originates from the presence of phenyl groups in the dimethylsiloxane (HP-5ms and 94

InertCap-17ms) or silarylene-siloxane polymer (DB-17ms) structure of the column coating. These 95

columns contain 5% or 50% phenyl groups. Phenyl groups have π electrons that have weak 96

hydrogen (H)-bond accepting properties. The DB-225ms column, with a coating of 50% 97

cyanopropylphenyl/50% dimethylsiloxane-equivalent silarylene-siloxane copolymer, contains a 98

polar nitrile group that acts as a H-bond acceptor. The polar property of the SolGel-WAX column 99

originates from the ether oxygen atoms in poly(ethylene glycol), which has strong H-bond 100

accepting properties. All columns had the dimension of 30 m 0.25 mm 0.25 μm. 101

102

Retention measurements 103

A program with linear oven temperature increase was applied on all columns until the 104

recommended maximum temperature was reached (240-300°C). Helium was used as carrier gas 105

and a flow rate of 1.2 mL/min was maintained throughout all measurements. Retention 106

measurements for SPB-Octyl, DB-17ms, DB-225ms, and SolGel-WAX were performed using cool 107

on-column injections on an Agilent 7890 GC, followed by atmospheric pressure chemical 108

ionization (APCI) and mass selective detection (Agilent 6530 QTOF-MS) (See Supplementary 109

Section S2 for the optimization of APCI-QTOF-MS parameters for CPs). An injection volume of 2 110

μL was used. The on-column injector temperature was kept at the initial oven temperature (60 111

or 70°C) for 0.1 min and increased with 100°C/min to the maximum oven temperature. The oven 112

temperature was kept at 60 or 70°C for 0.1 min and increased with 10°C/min to the maximum 113

temperature shown in Table 1. More details are stated in the Supplementary Section S2. 114

Retention measurements of SPB-Octyl and SolGel-WAX were also performed on a different 115

system (7890A/7000A triple quadrupole GC/MS, Agilent Technologies) and HP-5ms and InertCap-116

17ms only on this system because of its better availability in our laboratory. On the triple 117

quadrupole GC/MS system, splitless injection at 250°C and electron ionization (EI) were used. 118

Peak patterns were similar on both systems, and the retention indices (RIs; see below for the 119

definition) differed only by 7 on average and 20 in the worst case. In contrast to the EI-MS 120

detector, the APCI-QTOF-MS method allows for a detection of pseudo-molecular ions and thus 121

better identification of peaks that belong to the stated CP isomers. Therefore, if the 122

measurements were done on both systems, data from APCI-QTOF-MS were considered for the 123

latter discussions. Peak identifications for the EI-MS chromatograms of HP-5ms and InertCap-124

17ms were performed by using the APCI-TOF-MS chromatograms of SPB-Octyl and DB-17ms, 125

respectively, as reference, because the peak patterns were highly similar (see the results section). 126

127

Table 1. Polymer coating compositions of the GC columns and structures of the surrogate 128

molecules used in COSMOthermX. The circled parts (red) on the molecular fragments refer to the 129

groups that were disregarded using the weight string function in COSMOthermX. 130

GC system

Column Coating composition

according to

manufacturer

Manufacturer GC oven

temperature

program

GC system /

Detection

Fragments representing the polymer phase in

COSMOthermX

SPB-Octyl poly(50% n-octy/

50% dimethylsiloxane) Supelco

70 °C (1 min)

10 °C/min

280 °C (10 min)

Agilent 7890 GC /

Agilent 6530

QTOF-MS

HP-5ms poly(5% diphenyl/

95% dimethylsiloxane)

Agilent

Technologies

70 °C (0.1 min)

10 °C/min

280 °C (10 min)

Agilent 7890A GC/

Agilent 7000A

Triple Quad GC/MS

DB-17ms poly(50% phenyl/

50% dimethylsiloxane)1

Agilent

Technologies

60 °C (1 min)

10 °C/min

300 °C (10 min)

Agilent 7890 GC /

Agilent 6530

QTOF-MS

InertCap-17ms poly(50% diphenyl/

50% dimethylsiloxane) GL Sciences

70 °C (1 min)

20 °C/min

300 °C (10 min)

Agilent 7890A GC /

Agilent 7000A

Triple Quad GC/MS

DB-225ms

poly(50% cyano-

propylphenyl/ 50%

dimethylsiloxane) 1

Agilent

Technologies

70 °C (0.1 min)

10 °C/min

240 °C (15 min)

Agilent 7890 GC /

Agilent 6530

QTOF-MS

SolGel-WAX Polyethylene glycol SGE Analytical

Science

70 °C (1 min)

10 °C/min

280 °C (5 min)

Agilent 7890 GC /

Agilent 6530

QTOF-MS

1 Silarylene-siloxane copolymer; 2 Instead of 5 and 95% mole fractions, 5.3 and 94.7% was used as the liquid phase composition 131 for HP-5ms in COSMOthermX since the larger fragment contains not only diphenylsiloxane, but dimethylsiloxane as well. 132

133

RIs of CPs, n-alcohols, n-alkylmethyl esters, PAHs and n-alkanes were obtained using the 134

linear temperature-programmed retention index system (LTPRI). This system is used to establish 135

retention indices for retention times measured under a program with linear temperature 136

increase:13,14 137

138

1) 139

140

where Rti is the retention time of the analyte, Rtx is the retention time of the n-alkane eluting 141

directly before Rti, Rtx+1 is the retention time of the n-alkane eluting directly after Rti and RIx is 142

the retention index of the n-alkane that corresponds to Rtx. The retention indices of n-alkanes 143

are defined as its number of carbon atoms times a hundred. 144

145

ppLFER descriptors 146

ppLFERs are useful in characterizing interaction properties that determine partitioning 147

behavior of chemicals. ppLFERs are multiple linear regression models that use several solute 148

descriptors as independent variables for the calculation of partition coefficients.15 The most 149

frequently used ppLFER for the gas-condensed phase partitioning, established by Abraham et 150

al,16 has the general form: 151

152

log K = c + eE + sS + aA + bB + lL 2) 153

154

where log K is the logarithmic partition coefficient. The uppercase letters on the right-hand side 155

of the equation are the solute descriptors: E, excess molar refraction; S, dipolarity/polarizability 156

parameter; A, H-bond donating property; B, H-bond accepting property and L, logarithmic 157

hexadecane-air partition coefficient. The lowercase letters are the system parameters. Each term 158

quantitatively describes the energetic contribution of a molecular interaction to log K. Since none 159

of the columns from the current study has H-bond donating properties, the bB term can be 160

ignored. Solute descriptors S and A are both responsible for the polar interactions of the 161

chemical: S is related to the surface electrostatic property and is thought to represent polar 162

interactions that result in part from the partial charge distribution over the molecular surface.17 163

A reflects more specific interactions resulting from H-bond donating sites of the solute molecule. 164

The L solute descriptor describes the non-specific van der Waals interactions and also includes 165

the energy needed for cavity formation.15,18 The eE term also describes the van der Waals 166

interactions but usually has only minor contributions to log K. For more detailed explanations of 167

the equation, we refer to refs 13-15. 168

𝑅𝐼 =𝑅𝑡𝑖 − 𝑅𝑡𝑥𝑅𝑡𝑥+1 − 𝑅𝑡𝑥

× 100 + 𝑅𝐼𝑥

In this study, temperature-programmed RIs instead of log K are correlated with the 169

ppLFER descriptors. Because temperature-programmed RI is related but not directly proportional 170

to log K,19 the use of ppLFER for the RI is an approximation. For a more accurate investigation, 171

isothermal retention measurements would be better suited, although much more time-172

consuming than temperature-programmed measurements, as isothermal measurements must 173

be performed at many temperatures to cover diverse CP structures. The purpose of using 174

ppLFERs in the current work is to compare semi-quantitatively the polar interaction properties of 175

CP congeners with varying structures and not to derive accurate solute descriptors that could be 176

used for later predictions. 177

178

Prediction of RI with COSMOthermX 179

COSMOthermX software is based on the COSMO-RS theory, which uses quantum 180

mechanics and statistical thermodynamics calculations to determine the chemical potential of a 181

solute in solution and can thereby predict partition coefficients. Gas-GC coating (i.e., air-polymer) 182

partition coefficients were predicted following the method by Goss (2011).20 Molecular 183

structures of CPs, reference compounds and polymer coatings were expressed with SMILES 184

strings, which were then converted to SDF files. Quantum chemical calculations and conformer 185

selection were performed using COSMOconfX (version 4.3, COSMOlogic) with TURBOMOL 7.3, 186

which yield a complete set of relevant conformations with full geometry optimization in the gas 187

phase and in the conductor reference state. The gas phase energy and COSMO files of the CPs 188

and reference compounds were then used in the COSMOthermX software (version 19.04; 189

parameterization: BP_TZVPD_FINE_19) to calculate air-polymer partition coefficients (Kair-polymer). 190

To represent the molecular structure of polymer coating, monomers or oligomers of the coating 191

polymer structure provided by the manufacturer were used. For the quantum chemical 192

calculations performed by COSMOconfX, the end groups of these monomer or oligomer were 193

end-capped with CH3 groups. The CH3 groups were later disregarded during COSMOthermX 194

calculations by giving a weighting factor of 0, following the approach by Goss (2011).20 All these 195

surrogate structures used for coating polymers are shown in Table 1. The polymer structure of 196

the HP-5ms column consists of 5% diphenylsiloxane and 95% dimethylsiloxane and we 197

represented this structure with a mixture of diphenylsiloxane and dimethylsiloxane in the 198

respective mole fractions (see Table 1) in the COSMOthermX calculations. For the SolGel-WAX 199

column, an end-capped trimer of ethylene glycol was used, as in ref 17. 200

All calculations in COSMOthermX were performed with the combinatorial term switched 201

off, as is recommended for polymer by the COSMOthermX user guide.22,23 All conformers 202

generated by COSMOconfX of the target chemicals were used for the calculation of air-polymer 203

partition coefficients. However, to reduce calculation times, only the top 5 low-energy 204

conformers returned by COSMOconfX (_c0 to _c4 suffixes) were selected to represent the 205

polymer phases. For some CPs, COSMOconfX returned conformers with R or S configurations that 206

were inconsistent with the input structure. This problem did not occur when we turned off RDKit 207

and only used Balloon for the generation initial conformers on the Windows version of 208

COSMOconfX. 209

For each chemical and coating phase, Kair-polymer was predicted at 5 temperature steps 210

between 373.15 and 573.15 K. Then, linear regression between log Kair-polymer and 1/T was 211

established, and a hypothetical eluting temperature was interpolated at a column-specific, 212

characteristic Kair-polymer value that is derived from experimental data. This eluting temperature 213

was considered analogous to the retention time and used to derive RI, following eq 2. A more 214

detailed explanation about how RI values were predicted from COSMOthermX calculations is 215

presented in the Supplementary Section S1. 216

Because the stereometric structure of the isomers present in the CP standards is unknown, 217

partition coefficients were calculated for all possible diastereomers using COSMOthermX. A pair 218

of enantiomers was represented by a single structure in the COSMOthermX calculation, because 219

partition coefficients of enantiomers are the same in isotropic phases. The predictability of the 220

COSMOthermX program was tested by comparing the mean of predicted RIs for all possible 221

diastereomers and the weighted mean of the measured RI values of the CP standards from the 222

GC system. RI values of PAHs were calculated but not used in testing the predictability of 223

COSMOthermX, as their predicted RI values were systematically deviated from the measured 224

values (see Supplementary Table S4). 225

226

227

Results and discussion 228

Determination of GC retention times and RI 229

Retention measurements showed the presence of multiple peaks in most of the CP 230

analytical standards. Generally, CP congeners with a high number of possible diastereomers given 231

their molecular structure showed multiple peaks with a substantial peak area of the same 232

(pseudo)molecular ion. For example, on the SPB-Octyl column, 10 peaks within a minute of 233

retention time were found for 1,2,3,4,5,6-C11Cl6, which has 10 possible diastereomers (a pair of 234

enantiomers are considered one structure). In contrast, 1,1,1,3,9,10-C10Cl6 (2 possible 235

diastereomers) only showed one peak (Supplementary Fig. S1A and S1B). For one standard, 236

2,5,6,9-C10Cl4 (6 possible diastereomers), the manufacturer-provided certificate of analysis 237

stated the presence of three diastereomers without details on the exact stereometric structure 238

(e.g., S and R notation). While we indeed observed three peaks on the nonpolar SPB-Octyl column, 239

7 peaks were found on the most polar SolGel-WAX column (Fig. 1), showing increased separation 240

through polar interactions. As exceptional cases, 1,2,5,6,9,10-C10Cl6 (6 possible diastereomers) 241

only showed one peak on all columns (Supplementary Fig. S1C) and 2,3,4,5,6,7,8,9-C10Cl8 (72 242

possible diastereomers) showed 3 peaks on the SPB-Octyl column, and only 1 peak on the SolGel-243

WAX (Supplementary Fig. S1D). These standards likely contain a limited number of diastereomers. 244

Some CP standards with only few or no possible diastereomers resulted in a higher number of 245

peaks. For example, 1,1,1,3-C10Cl4 (no diastereomer) showed 5 peaks over 3 minutes of retention 246

time on the SPB-Octyl column (Supplementary Fig. S1E) and 4 peaks over 5 minutes of retention 247

time on the SolGel-WAX column. Most of the peaks in these chromatograms were small and are 248

likely constitutional isomers (i.e., impurities). 249

250

251 Figure 1. The Chromatogram of 2,3,6,9-C10Cl4 measured on the SolGel-WAX column. The 252

manufacturer-provided certificate of analysis of this analytical standard stated the presence of 253

three diastereomers. 254

255

As a representative RI value for a CP congener with multiple peaks, the mean of the RI 256

values weighted by the peak areas was calculated and used in the following discussions. While 257

we are aware that peak areas do not always reflect the relative abundance of CP isomers 258

present,24 this approach deemed better than simply calculating the mean of RIs for all peaks 259

without weighting, particularly in cases where one or a few major peaks appear with many small 260

peaks. 261

We note that no retention times of 1,1,1,3,11,12-C12Cl6, 1,1,1,3,9,10,10,10-C10Cl8 and 262

1,5,5,6,6,10-C10Cl6 could be determined on the SolGel-WAX column, as their peaks were broad 263

and the response was low (Supplementary Fig. S1F). This peak broadening is probably because of 264

thermal degradation, as a high temperature (280°C) was needed to elute these congeners. 265

Indeed, 1,5,5,6,6,10-C10Cl6 and 1,1,1,3,9,10,10,10-C10Cl8 were detected on the other highly polar 266

column DB-225ms, for which a lower temperature (240°C) for elution was applied. 267

268

Comparison of RIs on polar and nonpolar columns 269

Since polar compounds are retained more by polar coatings, comparing RI values between 270

columns of different polarity allows for the characterization of the polar interaction properties 271

of CP molecules and substructures. RIs of CPs on polar columns were always higher than those 272

on the nonpolar SPB-Octyl column, showing the significance of polar interaction properties for 273

all CP standards (Fig. 2). The range of RIs (or separation of diastereomer/constitutional isomer 274

peaks) for each CP standard was usually greater on polar columns, meaning that the isomers are 275

better separated with polar retention mechanisms instead of van der Waals interactions only. 276

A series of CP congeners with -CH2- increments show that RI on all columns increased with 277

102 to 119 per addition of -CH2- to the alkyl chain. These values are similar to the RI values of n-278

alcohols (102–107 per methylene) and n-alkylmethyl esters (100–105 per methylene, see 279

Supplementary Fig. S2). 280

Chlorine substitution on the alkyl chain generally increased RI to an extent depending on 281

the column polarity and the position of Cl. For example, the RI of 1,2,9,10-C10Cl4 on the SPB-Octyl 282

column is greater by 229 than that of a constitutional isomer 1,1,1,3-C10Cl4. The retention on the 283

SPB-Octyl column is driven by van der Waals interactions, which are correlated to the molecular 284

surface area of the molecule.25 The four Cl atoms of 1,2,9,10-C10Cl4 are distributed over the alkyl 285

chain and increase the molecular surface area more than the four Cl atoms of 1,1,1,3-C10Cl4 that 286

are shifted on one side. 287

Figure 2B shows ΔRI, defined as the RI of a column subtracted by the RI of SPB-Octyl to 288

clarify the contributions of polar interactions to the retention. Larger ΔRI values are observed 289

with increasing column polarity, while the trends of ΔRI over different congeners are similar for 290

all columns. Generally, a single Cl substitution on -CH2- to -CHCl- increases the polarity of CPs. 291

However, actual contributions appear to depend strongly on the neighboring structure of the -292

CHCl- group. A vicinal substitution pattern (-CHCl-CHCl-) does not increase the polarity so much 293

as an isolated -CHCl-. This is clearly shown with 2,3,4,5,6,7,8,9-C10Cl8, which shows only an 294

intermediate ΔRI although having the highest number of -CHCl- units. In a vicinal substitution 295

pattern, the proximity of -CHCl- groups might interfere with, and lower, the polarity and/or H-296

bond properties of a neighboring -CHCl- group. In contrast, a single Cl substitution on a terminal 297

carbon (-CH3) is less influenced by Cl on the neighboring carbon. Comparison of the 5 tetrachloro 298

(Cl4) congeners is illustrative for these trends: 2,5,6,9-C10Cl4 (2 isolated Cl and a pair of vicinal Cl) 299

and 1,2,9,10-C10Cl4 (2 pairs of vicinal Cl at the ends) show the highest ΔRI, followed by 4,5,7,8- 300

C11Cl4 (2 pairs of vicinal Cl) and 2,3,4,5-C10Cl4 (4 consecutive, vicinal Cl). 1,1,1,3-C10Cl4 is the least 301

polar of the measured CPs even though it contains one isolated -CHCl- group. This shows that 302

CCl3 has a much smaller contribution to polarity than 3 -CHCl-. It is interesting to note that ΔRI 303

of 1,1,1,3-C10Cl4 is about half that of 1,1,1,3,9,10,10,10-C10Cl8. As the latter has double the CCl3-304

CH2-CHCl- substitution pattern, this observation suggests that the additivity principle may hold 305

for the polarity of CPs, provided that the two structural units are far enough apart. The highest 306

ΔRI was observed for 1,2,5,6,9,10-C10Cl6 (3 pairs of vicinal Cl, of which 2 pairs at the ends). 307

1,5,5,6,6,10-C10Cl6 is the only CP standard with double chlorinated carbons and shows the second 308

highest ΔRI. Comparison to 1,2,5,6,9,10-C10Cl6 suggests that -CCl2-CCl2- may be less polar than 4 309

chlorines all as vicinal -CHCl- groups. Overall, the total number of -CHCl- groups is not decisive for 310

the polarity of CPs and the chlorination pattern needs to be considered. 311

312

313 Figure 2. The measured RI on GC columns (A), the measured RIs subtracted by the measured RI 314

on the SPB-Octyl column (ΔRI) (B), and RI values predicted by COSMOthermX subtracted by 315

predicted RI values of the SPB-Octyl column (C) for a selection of CP standards. The compounds 316

are ordered according to the ΔRI for DB-225ms (polar column with data available for most CPs). 317

The vertical error bars in panels A and B show the range of measured RIs for multiple peaks, 318

while the vertical error bars in panel C show the range of predicted RI values for CPs with 319

multiple diastereomers. Corrections were applied to predicted RIs (see text). 320

321

Describing polarity using ppLFERs 322

To investigate the types and the extent of polar interactions with CPs, ppLFER solute 323

descriptors were derived. The A and S descriptors describe the polarity of the CPs relevant for GC 324

retention times. First, the E values of CPs were obtained using the structure based estimation 325

method from the UFZ-LSER database,26 because E has been considered a simple additive 326

property.16 The E values obtained are presented in Supplementary Table S3a. Second, L values 327

were determined from SPB-Octyl data. The SPB-Octyl column exerts minimal polar interactions, 328

and system parameters s and a were therefore set to 0. Thus, 329

330

RI = c + eE + lL 3) 331

332

Here, the measured RI values and the solute descriptors (E, L) of n-alcohols, n-alkylmethyl esters, 333

n-alkanes and PAHs (Table 2b) were used to calibrate system parameters (c, e, l) for SPB-Octyl by 334

least-square multiple linear regression. The result is given in Supplementary Table S2. The solute 335

descriptors for these chemicals were obtained from the UFZ-LSER database.26 Then, from the 336

system parameters and E and RI values of CPs, L values were calculated (Supplementary Table 337

S3a): 338

339

L = (RI – c – eE)/l 4) 340

341

The A and S solute descriptors of CPs were calculated from the rest of the data. The 342

ppLFER model fit the calibration data well with R2 of 0.995-0.997 and the standard deviation (SD) 343

of 36-59. System parameters for all columns were qualitatively in good agreement with those 344

reported by Poole et al. using isothermal measurements (Supplementary Table S2). The a and s 345

system parameters are in the order of the expected polarity of the columns: SPB-Octyl < HP-5ms 346

<< DB-17ms < InertCap-17ms << DB-225ms < SolGel-WAX. The ppLFER equations for the columns 347

were transformed into: 348

349

RI – c – eE – lL = sS + aA 5) 350

351

S and A were determined from multiple linear regression with 0 intercept. The results are given 352

in Supplementary Fig. S3. The standard errors of S and A were relatively high. This can be 353

because of the incompatible results for the two most polar columns, DB-225ms and SolGel-354

WAX. As the e, a and s system parameters of the SolGel-WAX column are higher than those of 355

the DB-225ms column, one would expect that RIs on the SolGel-WAX column would also be 356

higher for all CPs. However, as Fig. 2 shows, RIs for SolGel-WAX were just as much as or even 357

lower than those for DB-225ms. These conflicting results may cause a relatively large error in A 358

and S. 359

As an attempt, we obtained A and S with the RI data for all but the SolGel-WAX column 360

and for all but the DB-225ms column. While the resulting A and S descriptor values differ (on 361

average 0.40 and 0.16, respectively), the trend across CP congeners remains the same between 362

the two approaches (Fig. 3). The S descriptor generally increased with the number of chlorinated 363

carbons. The lowest values were found for 1,1,1,3-C10Cl4 and highest for 1,2,5,6,9,10-C10Cl6 and 364

2,3,4,5,6,7,8,9-C10Cl8 (Fig. 3 and Supplementary Table S2). The A solute descriptor values were 365

not related to the number of chlorines but rather to specific chlorination patterns. Substructures 366

-CH2Cl and -CHCl- tend to increase A, but with the striking exception that compounds with 367

consecutive -CHCl- structures (i.e., 2,3,4,5-C10Cl4 and 2,3,4,5,6,7,8,9-C10Cl8) had lower A 368

descriptor values compared to CPs with the same number but a more distributed chlorination 369

pattern (i.e., 4,5,7,8-C11Cl4, 2,5,6,9-C10Cl4 and 1,2,5,6,9,10-C10Cl6). The differences in ΔRI between 370

constitutional isomers observed in the previous section are thus more related to H-bond 371

donating properties (A) of the isomers. 372

The polar property of chlorinated carbon moieties stems from the high electronegativity 373

of the Cl atom compared to that of the C atom. In a -CHCl- structure, the relatively high electron 374

affinity of Cl has an inductive effect on C which results in a positive partial charge on the H atom. 375

This makes the -CHCl- structure polar (positive S) and the H atom is then prone to act as a H-bond 376

donor (positive A). Such an inductive effect of Cl and the resulting H-bond donor property are 377

well known for small chloroalkanes such as dichloromethane (A = 0.1) and chloroform (A = 0.15). 378

However, in CP structures with vicinal -CHCl-, the Cl atom is often in proximity of the H atom of 379

the neighboring -CHCl- structure which appear to diminish the ability of the H to fully act as a H-380

bond donor. Having 4 or more consecutive -CHCl- structures put each H atom in an even more 381

crowded environment and brings back A to near 0 (Fig. 3). This interpretation is consistent with 382

the existing knowledge on A for hexachlorocyclohexane (HCH) isomers. A values for α- and γ-383

HCHs are 0, whereas β-HCH poses a significant A value (0.12).27 Because of the different 384

rotational configurations of the six -CHCl- units, β-HCH can take a conformation that maximizes 385

the exposition of H atoms to the surrounding, whereas α- and γ-HCHs cannot do so. 386

A CCl3-CH2-CHCl- structure in 1,1,1,3-C10Cl4 has a minimal H-bonding property (see Fig. 3), 387

which may be only attributable to the single -CHCl-. The -CCl3 group has no H-bond donor site 388

and does not appear to make the neighboring -CH2- acidic (similar case for 1,1,1-trichloroethane 389

with A = 0). However, a single Cl on the terminal carbon in a CH2Cl-CHCl- structure adds to H-390

bond donating properties of the CP (see A of 1,1,1,3-C10Cl4 < 1,1,1,3,9,10-C10Cl6). 1,2,3,4,5,6-391

Cl10Cl6 also contains this substructure although A is low, possibly due to steric effects or 392

interference from the neighboring consecutive CHCl structure. 393

The inconsistent results for SolGel-WAX and DB-225ms can have several causes. For 394

example, n-alkanes might undergo interfacial adsorption and can be retained under a mixed-395

mode retention mechanism on polar columns, which makes n-alkanes less suitable as reference 396

compounds for determining RI values.28 The exact reason is however difficult to conclude from 397

the current data. 398

399

400 Figure 3. Solute descriptors E, A, S and L for a selection of CPs. S and A descriptors were 401

determined using RI values from all columns while omitting either the SolGel-WAX or the DB-402

225ms column. Doing so has no influence on the determined E and L descriptor values. 403

404

COSMOthermX predictions 405

The COSMOthermX-predicted RIs correlated well with the measured RIs of CPs with an R2 406

between 0.975 and 0.995 (Supplementary Fig. S4). There is even high 1:1 agreement between 407

predicted and measured RIs for SPB-Octyl, HP-5ms, and SolGel-WAX (RMSE: 44-72). The 408

agreement, however, was lower for the columns DB-17ms, InertCap-17ms and DB-225ms (RMSE: 409

222-280). The CP group shows a trend that is not parallel to n-alkanes for these three columns 410

(Supplementary Fig. S4), and thus the discrepancy increases with increasing RI value. The polymer 411

coating of these columns contains a high proportion of phenyl groups (50% phenyl or diphenyl 412

groups) and, apparently, the interaction properties of these groups with the CP structures is not 413

fully captured by COSMOthermX. To make use of the high correlations between predicted and 414

measured RIs, we applied an empirical correction to the predicted RI values by using the 415

regression formula of predicted vs measured RI values for CPs (Supplementary Fig. S5). The 416

results are shown in Fig. 4 and Supplementary Fig. S5. The RSME values after correction were 417

between 21 and 75. 418

ΔRI values were calculated using the predicted RIs to test whether COSMOthermX can 419

capture differences in polarity between CP congeners (Fig. 2C). Comparing Fig. 2B and 2C 420

indicates that the overall trend agrees well with the experimentally observed ΔRIs. Thus, 421

COSMOthermX correctly reflects polarity differences between CPs with differing chlorination 422

patterns. The only discrepancy appears that COSMOthermX slightly overestimates the ΔRI values 423

of CPs with many consecutive -CHCl- groups (i.e., 1,2,3,4,5,6-C11Cl6 and 2,3,4,5,6,7,8,9-C10Cl8). 424

This statement however is conditional, because these two congeners have many possible 425

diastereomers (16 and 70, respectively), for which COSMOthermX calculated a relatively wide 426

range of ΔRIs. Currently, we do not know which diastereomers are present in the analytical 427

standards. 428

429

430 Figure 4. The RI values for CP congeners predicted by COSMOthermX for all columns in this 431

study against the measured RI values from the GC system. Empirical corrections were applied to 432

RI predictions (see text). 433

434

Effects of diastereomerism 435

The range of predicted RI values by COSMOthermX shown in Supplementary Fig. S4 and 436

S5 indicates the potential effects of diastereomerism of the CP on the partition properties (e.g., 437

2,3,4,5,6,7,8,9-C10Cl8). COSMOthermX predicts an increasing range of RI with increasing polarity 438

of the polymer phase, which was also observed in the retention measurements on the GC 439

systems. While CPs with many possible diastereomers usually showed a wide range in measured 440

0

1000

2000

3000

4000

0

1000

2000

3000

4000

Measured RI

Pre

dic

ted

RI

HP-5msDB-17msInertCap-17msDB-225ms

SPB-Octyl

SolGel-WAX

RI values, predicted RI values often span over an even wider range, suggesting that not all 441

possible diastereomers are present in the CP standards. Comparing the two diastereomers of 442

2,3,4,5,6,7,8,9-C10Cl8, with the highest and lowest predicted RI values on the DB-225ms column 443

((2R,3S,4S,5S,6S,7S,8S,9R)-2,3,4,5,6,7,8,9-C10Cl8 and (2R,3R,4S,5S,6S,7S,8R,9R)-2,3,4,5,6,7,8,9-444

C10Cl8, predicted RI of 2721 and 2304, respectively), we can see that a difference in rotational 445

configurations around the chiral carbons can result in distinctly different three-dimensional 446

shapes (Fig. 5). Overall, according to the results from COSMOthermX, the difference between 447

diastereomers can greatly affect the 3D-structure of the CP molecules, which, in turn, affects the 448

interaction properties of the molecule and its partition behavior. 449

450

451 452

Figure 5. The lowest-energy conformers (_c0 suffix) of (2R,3S,4S,5S,6S,7S,8S,9R)-2,3,4,5,6,7,8,9-453

C10Cl8 (A) and (2R,3R,4S,5S,6S,7S,8R,9R)-2,3,4,5,6,7,8,9-C10Cl8 (B), generated by COSMOconfX. 454

Both are diastereomers of 2,3,4,5,6,7,8,9-C10Cl8. 455

456

Conclusions 457

Inspection of RI values of CPs from GC columns with different polarity shows that the 458

chlorination pattern plays an important role in determining polar interactions of CPs. Isolated -459

CHCl- groups or a pair of two vicinal -CHCl- are more polar than patterns with three or more 460

consecutive -CHCl- groups. Polarity is also increased when a single Cl atom is present at the 461

terminal carbon (e.g., -CH2Cl), whereas three Cl atoms at the terminal (-CCl3) add least to polarity 462

of the CP molecules. 463

Determining ppLFER descriptors for CPs shows that polarity differs significantly between 464

CP chlorination patterns and confirm the importance of Cl positioning to the H-bond donating 465

properties (A) of CPs. The calculated solute descriptors show that H-bond interactions are lower 466

for CPs with many consecutive -CHCl- groups than for CPs with a more distributed chlorination 467

pattern. 468

Predictions from COSMOthermX show that the quantum chemically based modelling 469

approach is capable of predicting RI values and can reflect the effect of variations in chlorination 470

pattern on the interaction properties of CPs. This result supports the general accuracy of 471

COSMOthermX to predict partition coefficients of CPs. As future work, retention time predictions 472

by COSMOthermX for a diverse set of congeners could be compared to measured chromatograms 473

of CPs in environmental samples or in complex technical mixtures to infer the congener 474

compositions present. 475

476

Data availability 477

The authors declare that all data supporting the findings of this study are available 478

within the article and its supplementary information file. 479

480

References 481

1. van Mourik, L. M., Gaus, C., Leonards, P. E. G. & de Boer, J. Chlorinated paraffins in the 482

environment: A review on their production, fate, levels and trends between 2010 and 2015. 483

Chemosphere 155, 415–428 (2016). 484

2. Tomy, G. T., Fisk, A. T., Westmore, J. B. & Muir, D. C. G. Environmental chemistry and toxicology of 485

polychlorinated n-alkanes. Rev. Environ. Contam. Toxicol. 158, 53–128 (1998). 486

3. Sverko, E., Tomy, G. T., Märvin, C. H. & Muir, D. C. G. Improving the quality of environmental 487

measurements on short chain chlorinated paraffins to support global regulatory efforts. Environ. Sci. 488

Technol. 46, 4697–4698 (2012). 489

4. Brandsma, S. H. et al. Chlorinated Paraffins in Car Tires Recycled to Rubber Granulates and 490

Playground Tiles. Environ. Sci. Technol. 53, 7595–7603 (2019). 491

5. Vorkamp, K., Balmer, J., Hung, H., Letcher, R. J. & Rigét, F. F. A review of chlorinated paraffin 492

contamination in Arctic ecosystems. Emerg. Contam. 5, 219–231 (2019). 493

6. ChemicalWatch. China updates severely restricted toxic chemicals catalogue. 1 494

https://chemicalwatch.com/87564/china-updates-severely-restricted-toxic-chemicals-catalogue 495

(2020). 496

7. Brandsma, S. H. et al. Medium-Chain Chlorinated Paraffins (CPs) Dominate in Australian Sewage 497

Sludge. Environ. Sci. Technol. 51, 3364–3372 (2017). 498

8. Nikiforov, V. A. Synthesis of Polychloroalkanes. in Chlorinated Paraffins (ed. de Boer, J.) 41–82 499

(2010). doi:10.1007/698_2009_40. 500

9. van Mourik, L. M. et al. The underlying challenges that arise when analysing short-chain chlorinated 501

paraffins in environmental matrices. J. Chromatogr. A 1610, 460550 (2020). 502

10. Yuan, B. et al. Accumulation of Short-, Medium-, and Long-Chain Chlorinated Paraffins in Marine 503

and Terrestrial Animals from Scandinavia. Environ. Sci. Technol. 53, 3526–3537 (2019). 504

11. Glüge, J., Bogdal, C., Scheringer, M., Buser, A. M. & Hungerbühler, K. Calculation of Physicochemical 505

Properties for Short- and Medium-Chain Chlorinated Paraffins. J. Phys. Chem. Ref. Data 42, 023103 506

(2013). 507

12. Endo, S. & Hammer, J. Predicting Partition Coefficients of Short-Chain Chlorinated Paraffin 508

Congeners by Combining COSMO-RS and Fragment Contribution Model Approaches. Preprint (2020) 509

doi:10.26434/chemrxiv.12525656. 510

13. Martos, P. a., Saraullo, A. & Pawliszyn, J. Estimation of Air/Coating Distribution Coefficients for Solid 511

Phase Microextraction Using Retention Indexes from Linear Temperature-Programmed Capillary 512

Gas Chromatography. Application to the Sampling and Analysis of Total Petroleum Hydrocarbons in 513

Air. Anal. Chem. 69, 402–408 (1997). 514

14. van Den Dool, H. & Dec. Kratz, P. A generalization of the retention index system including linear 515

temperature programmed gas-liquid partition chromatography. J. Chromatogr. A 11, 463–471 516

(1963). 517

15. Endo, S. & Goss, K. U. Applications of polyparameter linear free energy relationships in 518

environmental chemistry. Environ. Sci. Technol. 48, 12477–12491 (2014). 519

16. Abraham, M. H., Ibrahim, A. & Zissimos, A. M. Determination of sets of solute descriptors from 520

chromatographic measurements. J. Chromatogr. A 1037, 29–47 (2004). 521

17. Arey, J. S., Green, W. H. & Gschwend, P. M. The Electrostatic Origin of Abraham’s Solute Polarity 522

Parameter. J. Phys. Chem. B 109, 7564–7573 (2005). 523

18. Poole, C. F. & Poole, S. K. Separation characteristics of wall-coated open-tubular columns for gas 524

chromatography. J. Chromatogr. A 1184, 254–280 (2008). 525

19. Curvers, J., Rijks, J., Cramers, C., Knauss, K. & Larson, P. Temperature programmed retention indices: 526

Calculation from isothermal data. Part 1: Theory. J. High Resolut. Chromatogr. 8, 607–610 (1985). 527

20. Goss, K.-U. Predicting Equilibrium Sorption of Neutral Organic Chemicals into Various Polymeric 528

Sorbents with COSMO-RS. Anal. Chem. 83, 5304–5308 (2011). 529

21. COSMOlogic GmbH. COSMO-RS. (COSMOlogic, 2015). 530

22. COSMOlogic GmbH & Co. KG. COSMOthermX User Guide. (2016). 531

23. Goss, K.-U. Predicting Equilibrium Sorption of Neutral Organic Chemicals into Various Polymeric 532

Sorbents with COSMO-RS. Anal. Chem. 83, 5304–5308 (2011). 533

24. Schinkel, L. et al. Deconvolution of Mass Spectral Interferences of Chlorinated Alkanes and Their 534

Thermal Degradation Products: Chlorinated Alkenes. Anal. Chem. 89, 5923–5931 (2017). 535

25. van Noort, P. C. M., Haftka, J. J. H. & Parsons, J. R. A simple McGowan specific volume correction for 536

branching in hydrocarbons and its consequences for some other solvation parameter values. 537

Chemosphere 84, 1102–1107 (2011). 538

26. Ulrich, N. ; Endo, S. ;. Brown, T. N. ;. Watanabe, N. ;. Bronner, G. ;. Abraham, M. H. ;. Goss, K. U. UFZ-539

LSER database v 3.2 [Internet]. Available from http://www.ufz.de/lserd (2017). 540

27. Goss, K.-U., Arp, H. P. H., Bronner, G. & Niederer, C. Partition Behavior of Hexachlorocyclohexane 541

Isomers. J. Chem. Eng. Data 53, 750–754 (2008). 542

28. González, F. R., Castells, R. C. & Nardillo, A. M. Behavior of n-alkanes on poly(oxyethylene) capillary 543

columns: Evaluation of interfacial effects. J. Chromatogr. A 927, 111–120 (2001). 544

545

Author information 546

Corresponding author 547

Jort Hammer 548

Hammer.jort@nies.go.jp 549

ORCID: 0000-0002-1403-2631 550

551

552

Additional information 553

The authors declare no competing financial interest. 554

Supplementary information is available for this paper at... 555

556

Author contributions 557

Study design: JH, SE. GC-MS measurements: JH, HM. COSMO-RS calculations: JH. Data 558

evaluation: JH, SE. Drafting of manuscript: JH. Revising of manuscript: JH, SE, HM. 559

560

Acknowledgements 561

This research was supported by the Environment Research and Technology Development 562

Fund SII-3-1 (JPMEERF18S20300) of the Environmental Restoration and Conservation Agency, 563

Japan. COSMOconfX and TURBOMOL calculations were performed with the NIES supercomputer 564

system. We thank Kai-Uwe Goss for their valuable comments on the manuscript, and Yoshinori 565

Fujimine (Otsuka Pharmaceutical Co., Ltd.) for donating the standard solution of 1,5,5,6,6,10-566

C10Cl6. 567

568

download fileview on ChemRxiv20200803-CPs_GC-COSMO_Hammer-Endo.pdf (1.27 MiB)

Congener-specific partition properties of chlorinated paraffins

evaluated with COSMOtherm and gas chromatographic retention

indices

Jort Hammer*, Hidenori Matsukami, Satoshi Endo

National Institute for Environmental Studies (NIES), Center for Health and Environmental Risk

Research, Onogawa 16-2, 305-8506 Tsukuba, Ibaraki, Japan

*Corresponding author

Supporting Information

Section S1: Prediction of RI using COSMOthermX

The surrogate molecules of the column coatings used consisted of a monomer or an oligomer from the

polymer structure (see Table 1 in the manuscript). For the quantum-mechanical calculations performed

by COSMOconfX, these surrogate molecules were end-capped with CH3 groups. Later, for the calculation

of partition coefficients, these groups were disregarded using the weight string function in COSMOthermX.

Since the combinatorial term in the free energy of partitioning is not well defined for polymers, all

calculations were performed with the combinatorial term turned off. To predict RI values of all compounds,

the calculated air-polymer partition coefficients (Kair/polymer) from COSMOthermX need to be converted to

RIs. While temperature-programmed RI is related but not directly proportional to Kair/polymer,1 we opted a

simple empirical approach for this conversion as described below.

As the GC measurements were performed under a program with linear temperature increase, the

retention time corresponds to the elution temperature of each compound. In COSMOthermX, a linear

relationship between log Kair/polymer and the reciprocal of temperature (1/T) was obtained for each

compound by calculating partition coefficients at 5 different temperatures (Fig. S6). Using this linear

relationship, the experimentally obtained elution temperatures for reference compounds (n-alkanes, n-

alcohols, n-alkylmethylesters) were converted to log Kair/polymer values (Fig. S6A). The resulting log Kair/polymer

values were specific to the column and were similar across the reference compounds (average SD = 0.15

in the current study). Note that compounds that eluted after the maximum temperature of the GC

program was reached were removed from consideration. The mean of these “elution” log Kair/polymer values

for reference compounds was calculated and was used to back-calculate the predicted elution

temperatures for all compounds including CPs (Figure S6B). Finally, RI values were computed from these

calculated elution temperatures using a modified version of equation 1 (i.e., where retention times were

replaced by elution temperatures). Note that log Kair/polymer of long alkanes (> C26) were extrapolated from

shorter alkanes because COMSOconfX calculation times were too long (> 5 days).

Section S2: GC-APCI-QTOF-MS parameter optimization

The APCI-QTOF-MS parameters were optimized for the identification of CP isomers, which were

detected by APCI in positive mode. Intense pseudo-molecular ions of the CP isomers were observed

corresponding to the dechlorinated and deprotonated molecules (Figs. S7a and S7b). Fragmentor

voltage, capillary voltage, corona current and gas temperature for enhancing ionization (Fig. 8) were

optimized and set to 150 V, 2500 V, 1.0 μA, and 350 °C, respectively.

TABLES

Table S1. The analytical standards of CP isomers used in this study. (N.A., not available)

Supplier Cat No. Compound name Concentration

(μg/mL)

Purity

(%)

Dr Ehrenstorfer GmbH DRE-LA17356500CY 2,5,6,9-Tetrachlorodecane 10 98.3 Dr Ehrenstorfer GmbH DRE-LA14171500CY 1,2,5,6,9,10-Hexachlorodecane 10 99.9 Dr Ehrenstorfer GmbH DRE-ZA15705000CY 2,3,4,5,6,7,8,9-Octachlorodecane 1 99.9 Chiron AS 1662.10-100-IO 1,1,1,3-Tetrachlorodecane 100 99.9 Chiron AS 1649.11-100-IO 1,1,1,3-Tetrachloroundecane 100 97.3 Chiron AS 1651.12-100-IO 1,1,1,3-Tetrachlorododecane 100 94.5 Chiron AS 1653.13-100-IO 1,1,1,3-Tetrachlorotridecane 100 97.1 Chiron AS 1676.14-K-IO 1,1,1,3-Tetrachlorotetradecane 1000 N.A. Chiron AS 1622.10-100-IO 1,1,1,3,8,10,10,10-Octachlorodecane 100 96.4 Chiron AS 1623.11-100-IO 1,1,1,3,9,11,11,11-Octachloroundecane 100 99.9 Chiron AS 1624.12-100-IO 1,1,1,3,10,12,12,12-Octachlorododecane 100 97.7 Chiron AS 1625.13-100-IO 1,1,1,3,11,13,13,13-Octachlorotridecane 100 99.9 Chiron AS 1678.14-K-IO 1,1,1,3,12,14,14,14-Octachlorotetradecane 1000 N.A. Chiron AS 1671.10-100-IO 1,2,9,10-Tetrachlorodecane 100 95.4 Chiron AS 1674.11-100-IO 1,2,10,11-Tetrachloroundecane 100 N.A. Chiron AS 1677.14-K-IO 1,2,13,14-Tetrachlorotetradecane 1000 N.A. Chiron AS 12285.11-100-IO 1,2,3,4,5,6-Hexachloroundecane 100 62.5 Chiron AS 12728.11-100-IO 4,5,7,8- Tetrachloroundecane 100 89.4 Chiron AS 12590.10-100-IO 2,3,4,5-Tetrachlorodecane 100 71.6 Chiron AS 12425.12-100-IO 2,3,4,5-Tetrachlorododecane 100 67.1 CIL CIL-ULM-8917-1.2 1,5,5,6,6,10-Hexachlorodecane 100 95 Chiron AS 1659.10-100-IO 1,1,1,3,9,10-Hexachlorodecane 100 96.3 Chiron AS 1650.11-100-IO 1,1,1,3,10,11-Hexachloroundecane 100 99.9 Chiron AS 1652.12-100-IO 1,1,1,3,11,12-Hexachlorododecane 100 99.9 Chiron AS 1654.13-100-IO 1,1,1,3,12,13-Hexachlorotridecane 100 95

Table S2. System parameters e, a, s, l and c, and SD and R2 for the columns in this study calculated using

reference compounds. Values in parentheses are standard errors.

System parameters

Compounds e a s l c SD R2

SPB-Octyl 126 (±8) 0 0 202 (±1) 60 (±21) 36 0.997

HP-5ms 8 (±16) 212 (±27) 73 (±48) 203 (±1) 7 (±21) 39 0.996

DB-17ms 113 (±23) 401 (±40) 155 (±72) 205 (±2) -15 (±29) 59 0.994

InertCap-17ms 123 (±26) 438 (±46) 175 (±84) 205 (±2) -33 (±35) 62 0.993

DB-225ms 81 (±20) 644 (±31) 507 (±55) 206 (±2) -11 (±27) 44 0.994

SolGel-WAX 143 (±18) 691 (±29) 779 (±52) 203 (±2) 14 (±24) 41 0.995

Table S3a. The ppLFER solute descriptors for CPs whereof data was available from all columns (with an exception for 1,5,5,6,6,10-C10Cl6, which

was not detected on the SolGel-WAX). E values for CPs were obtained from the UFZ database and L was calculated using the SPB-Octyl column. A

and S values were calculated using either all columns without the DB-225ms column or without the SolGel-WAX column (see text for more

details). E, A, S and L values for n-alcohols, n-alkylmethyl esters, n-alkanes and PAHs were obtained from the UFZ database. (N.A., not available)

Compounds E A

(without SolGel-WAX) A

(without DB-225ms) S

(without SolGel-WAX) S

(without DB-225ms) L

1,1,1,3,10,11-C11Cl6 0.85 1.062 (±0.148) 0.353 (±0.091) 0.417 (±0.092) 0.692 (±0.080) 10.104

1,1,1,3,11,12-C12Cl6 0.85 1.092 (±0.139) -1.10 (±0.119) 0.392 (±0.086) 1.241 (±0.104) 10.674

1,1,1,3,12,13-C13Cl6 0.85 1.086 (±0.198) -1.11 (±0.150) 0.404 (±0.124) 1.256 (±0.131) 11.190

1,1,1,3,8,10,10,10-C10Cl8 1.04 1.124 (±0.165) -1.08 (±0.136) 0.370 (±0.103) 1.227 (±0.119) 10.679

1,1,1,3,9,10-C10Cl6 0.85 1.119 (±0.130) 0.391 (±0.083) 0.393 (±0.081) 0.676 (±0.073) 9.558

1,1,1,3-C10Cl4 0.52 0.267 (±0.026) 0.055 (±0.018) 0.323 (±0.016) 0.406 (±0.016) 7.483

1,1,1,3-C11Cl4 0.52 0.231 (±0.019) 0.040 (±0.014) 0.357 (±0.011) 0.432 (±0.012) 7.975

1,1,1,3-C12Cl4 0.52 0.297 (±0.032) 0.060 (±0.022) 0.315 (±0.020) 0.407 (±0.019) 8.524

1,1,1,3-C13Cl4 0.52 0.337 (±0.070) 0.079 (±0.039) 0.290 (±0.043) 0.390 (±0.034) 9.030

1,2,10,11-C11Cl4 0.65 1.079 (±0.086) 0.405 (±0.059) 0.413 (±0.054) 0.675 (±0.051) 8.978

1,2,3,4,5,6-C11Cl6 1.14 0.725 (±0.062) -0.03 (±0.015) 0.565 (±0.039) 0.858 (±0.013) 9.338

1,2,5,6,9,10-C10Cl6 0.99 1.787 (±0.107) 0.656 (±0.080) 0.455 (±0.067) 0.893 (±0.069) 9.898

1,2,9,10-C10Cl4 0.65 1.049 (±0.077) 0.411 (±0.054) 0.429 (±0.048) 0.677 (±0.047) 8.424

1,5,5,6,6,10-C10Cl6 0.81 1.045 (±0.000) N.A. 0.647 (±0.000) N.A. 10.054

2,3,4,5,6,7,8,9-C10Cl8 1.56 0.373 (±0.202) -0.11 (±0.098) 0.782 (±0.126) 0.968 (±0.085) 9.551

2,3,4,5-C10Cl4 0.74 0.398 (±0.084) 0.042 (±0.036) 0.454 (±0.052) 0.590 (±0.031) 7.433

2,3,4,5-C12Cl4 0.74 0.381 (±0.085) 0.028 (±0.038) 0.454 (±0.053) 0.590 (±0.033) 8.490

2,5,6,9-C10Cl4 0.59 1.092 (±0.051) 0.333 (±0.715) 0.420 (±0.031) 0.714 (±0.037) 7.930

4,5,7,8-C11Cl4 0.65 0.720 (±0.088) 0.129 (±0.038) 0.347 (±0.055) 0.575 (±0.033) 7.946

Table S3b. The solute descriptors E, A, S and L for the reference compounds used for the determination of system parameters for the GC-

columns in this study. Compound E A S L Compound E A S L

C8OH 0.2 0.37 0.42 4.619 C6OOC 0.08 0 0.6 3.874

C10OH 0.19 0.37 0.42 5.628 C8OOC 0.07 0 0.6 4.838

C12OH 0.18 0.37 0.42 6.62 C10OOC 0.05 0 0.6 5.803

C16OH 0.15 0.37 0.42 8.654 C12OOC 0.04 0 0.6 6.767

C18OH 0.15 0.37 0.42 9.662 C14OOC 0.03 0 0.6 7.731

C20OH 0.14 0.37 0.42 10.667 C16OOC 0.02 0 0.6 8.695

Decane 0 0 0 4.686 C18OOC 0.01 0 0.6 9.659

Undecane 0 0 0 5.191 C20OOC 0 0 0.6 10.75

Dodecane 0 0 0 5.696 C22OOC 0.05 0 0.6 11.82

Tridecane 0 0 0 6.2 C24OOC 0.05 0 0.6 12.824

Tetradecane 0 0 0 6.705 Naphthalene 1.23 0 0.91 5.157

Pentadecane 0 0 0 7.209 Acenaphthylene 1.55 0 1.13 6.395

Hexadecane 0 0 0 7.714 Acenaphthene 1.45 0 0.95 6.709

Heptadecane 0 0 0 8.218 Fluorene 1.66 0 1.1 6.948

Octadecane 0 0 0 8.722 Phenanthrene 1.92 0 1.28 7.712

Nonadecane 0 0 0 9.226 Anthracene 1.98 0 1.28 7.735

Eicosane 0 0 0 9.731 Fluoranthene 2.35 0 1.48 8.733

Henicosane 0 0 0 10.236 Pyrene 2.24 0 1.48 8.974

Docosane 0 0 0 10.74 Benz[a]anthracene 2.74 0 1.68 10.124

Tricosane 0 0 0 11.252 Chrysene 2.65 0 1.67 10.123

Tetracosane 0 0 0 11.758 Benzo[b]fluoranthene 3.19 0 1.82 11.632

Pentacosane 0 0 0 12.264 Benzo[k]fluoranthene 3.19 0 1.91 11.607

Hexacosane 0 0 0 12.77 Benzo[a]pyrene 3.02 0 1.85 11.54

Heptacosane 0 0 0 13.276

Octacosane 0 0 0 13.78

Nonacosane 0 0 0 14.291

Triacontane 0 0 0 14.794

Table S4. Weighted mean and range of RI values of n-alcohols, n-alkylmethyl esters, PAHs and CPs for SPB-Octyl, HP-5ms, DB-17ms, InertCap-

17ms, DB-225ms and SolGel-WAX colums. (N.A., not available) Compounds (number of possible diastereomers)

SPB-Octyl HP-5ms DB-17ms InertCap-17ms DB-225ms SolGel-WAX

Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI

C8OH 1015 1113 1068 1073 1174 1120 1106 1392 1205 1551 1413

C10OH 1220 1305 1272 1276 1382 1314 1388 1304 1604 1424 1755 1658

C12OH 1425 1496 1474 1474 1587 1508 1595 1507 1817 1633 1958 1863

C16OH 1836 1895 1882 1881 2000 1909 2009 1920 2247 2040 2370 2294

C18OH 2041 2104 2085 2087 2207 2119 2218 2136 2459 2245 2577 2486

C20OH 2245 2295 2289 2287 2410 2312 2434 2329 2673 2499 2786 2674

C8OOC 1071 1124 1123 1121 1226 1158 1229 1180 1347 1228 1393 1351

C10OOC 1273 1301 1324 1306 1427 1341 1446 1360 1556 1437 1596 1534

C12OOC 1474 1511 1525 1514 1628 1553 1644 1574 1765 1659 1802 1762

C14OOC 1675 1741 1726 1734 1836 1771 1847 1792 1975 1864 2008 1981

C16OOC 1876 1927 1927 1927 2040 1964 2050 1984 2186 2080 2215 2214

C18OOC 2076 2130 2128 2127 2243 2167 2254 2187 2397 2268 2421 2385

C20OOC 2277 2317 2330 2318 2447 2351 2458 2367 2607 2562 2630 2612

C22OOC 2477 2514 2531 2522 2652 2571 2662 2597 2816 2664 2838 2798

C24OOC 2678 2686 2733 2697 2856 2728 2868 2739 3023 2943 3043 2985

Naphthalene 1206 1198 1193 1156 1420 1420 1431 1214 1615 1288 1754 1469

Acenaphthylene 1489 1457 1463 1403 1767 1455 1795 1482 2048 1643 2209 1878

Acenaphthene 1529 1436 1498 1385 1796 1431 1827 1459 2027 1577 2156 1769

Fluorene 1630 1553 1598 1488 1914 1542 1951 1577 2196 1687 2353 1931

Phenanthrene 1854 1830 1800 1746 2192 1816 2247 1852 2571 2040 2747 2381

Anthracene 1865 1815 1810 1733 2206 1802 2257 1837 2578 2012 2752 2347

Fluoranthene 2163 2057 2087 1950 2569 2036 2644 2091 3010 2299 3221 2704

Pyrene 2236 2052 2143 1940 2667 2027 2749 2082 3090 2290 3319 2694

Benz[a]anthracene N.A. 2316 2486 2255 3088 2337 3186 2391 N.A. 2596 N.A. 3000

Chrysene N.A. 2426 2497 2304 3127 2396 3216 2458 N.A. 2713 N.A. 3253

Benzo[b]fluoranthene N.A. 2543 2812 2392 3499 2488 3587 2564 N.A. 2718 N.A. 3294

Benzo[k]fluoranthene N.A. 2528 2820 2387 3513 2480 3596 2552 N.A. 2750 N.A. 3267

Benzo[a]pyrene N.A. 2550 2906 2392 3647 2490 3724 2569 N.A. 2721 N.A. 3302

Dibenzo[ah]anthracene N.A. 2896 3224 2798 N.A. 2908 4072 2969 N.A. 3229 N.A. 3839

Indeno[1,2,3-cd]pyrene N.A. 2729 3232 2675 N.A. 2770 N.A. 2831 N.A. 3074 N.A. 3572

Benzo[ghi]perylene N.A. 2753 3290 2695 N.A. 2795 4179 2859 N.A. 3105 N.A. 3613

Table S4. (Continued)

Compounds (nmber of diastereomers)

SPB-Octyl HP-5ms DB-17ms InertCap-17ms DB-225ms SolGel-WAX

Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI

1,1,1,3,9,10-C10Cl6 (4) 2089

(2089 - 2089) 2143

(2104 - 2161) 2091

(2091 - 2091) 2115

(2078 - 2132) 2370

(2286 - 2396) 2389

(2342 - 2410) 2406

(2406 - 2406) 2427

(2377 - 2450) 2838

(2838 - 2838) 2796

(2732 - 2826) 2838

(2838 - 2839) 2868

(2808 - 2895)

1,1,1,3,10,11-C11Cl6 (4) 2199

(2148 - 2204) 2247

(2213 - 2272) 2199

(2146 - 2202) 2236

(2200 - 2264) 2488

(2404 - 2488) 2508

(2467 - 2541) 2516

(2443 - 2522) 2546

(2502 - 2582) 2937

(2846 - 2950) 2947

(2858 - 3011) 2931

(2830 - 2949) 2973

(2900 - 3034)

1,1,1,3,11,12-C12Cl6 (4) 2314

(2260 - 2315) 2319

(2302 - 2358) 2314

(2314 - 2314) 2322

(2309 - 2357) 2595

(2493 - 2631) 2593

(2571 - 2641) 2630

(2354 - 2636) 2632

(2608 - 2685) 3053

(2959 - 3057) 3030

(2999 - 3089) N.A.

3031 (2981 - 3117)

1,1,1,3,12,13-C13Cl6 (4) 2418

(2369 - 2421) 2415

(2400 - 2457) 2407

(2163 - 2423) 2420

(2407 - 2456) 2709

(2562 - 2743) 2706

(2687 - 2757) 2743

(2628 - 2751) 2751

(2730 - 2801) 3163

(3067 - 3168) 3126

(3103 - 3188) N.A.

3134 (3106 - 3207)

1,1,1,3,14,15-C15Cl6 (4) 2633

(2633 - 2633) 2639

(2625 - 2664) 2627

(2376 - 2663) 2638

(2612 - 2683) 2930

(2858 - 2969) 2961

(2942 - 2993) 2976

(2850 - 3020) 3002

(2983 - 3036) N.A.

3352 (3317 - 3413)

N.A. 3332

(3295 - 3399)

1,1,1,3,8,10,10,10-C10Cl8 (3) 2322

(2322 - 2322) 2327

(2305 - 2340) 2309

(2309 - 2324) 2312

(2293 - 2324) 2590

(2381 - 2627) 2593

(2569 - 2607) 2644

(2644 - 2644) 2621

(2596 - 2637) 3061

(3061 - 3061) 3050

(3026 - 3064) N.A.

3097 (3066 - 3116)

1,1,1,3,9,11,11,11-C11Cl8 (3) 2437

(2437 - 2437) 2403

(2393 - 2419) 2425

(2409 - 2443) 2393

(2384 - 2410) 2715

(2499 - 2752) 2683

(2672 - 2704) 2758

(2585 - 2808) 2719

(2707 - 2739) N.A.

3126 (3112 - 3144)

N.A. 3177

(3159 - 3195)

1,1,1,3,10,12,12,12-C12Cl8 (3) 2546

(2546 - 2546) 2545

(2512 - 2564) 2526

(2272 - 2540) 2523

(2502 - 2536) 2763

(2763 - 2763) 2858

(2828 - 2875) 2883

(2693 - 2889) 2911

(2878 - 2931) N.A.

3285 (3262 - 3297)

N.A. 3319

(3298 - 3331)

1,1,1,3,11,13,13,13-C13Cl8 (3) 2654

(2654 - 2654) 2652

(2648 - 2655) 2620

(2381 - 2651) 2639

(2633 - 2646) 2955

(2927 - 3009) 2971

(2967 - 2976) 2958

(2686 - 3046) 3009

(3004 - 3013) N.A.

3396 (3388 - 3402)

N.A. 3414

(3408 - 3420)

1,1,1,3,12,14,14,14-C14Cl8 (3) 2764

(2764 - 2764) 2751

(2718 - 2793) 2746

(2490 - 2762) 2774

(2747 - 2807) 3065

(2780 - 3108) 3100

(3060 - 3148) 3116

(2994 - 3160) 3142

(3101 - 3192) N.A.

3554 (3507 - 3611)

N.A. 3552

(3509 - 3607)

1,1,1,3-C10Cl4 (2) 1622

(1606 - 1856) 1606

(1606 - 1606) 1615

(1615 - 1615) 1615

(1615 - 1615) 1734

(1734 - 1849) 1748

(1748 - 1748) 1749

(1749 - 1749) 1760

(1760 - 1760) 1906

(1828 - 2094) 1918

(1918 - 1918) 1916

(1908 - 1917) 1866

(1866 - 1866)

1,1,1,3-C11Cl4 (2) 1721

(1651 - 1723) 1723

(1723 - 1723) 1721

(1721 - 1721) 1734

(1734 - 1734) 1844

(1763 - 1844) 1885

(1885 - 1885) 1856

(1856 - 1856) 1899

(1899 - 1899) 2011

(1930 - 2012) 2054

(2054 - 2054) 2022

(1994 - 2024) 2010

(2010 - 2010)

1,1,1,3-C12Cl4 (2) 1832

(1800 - 1896) 1819

(1819 - 1820) 1826

(1826 - 1826) 1843

(1842 - 1844) 1948

(1755 - 2063) 1999

(1998 - 2000) 1965

(1939 - 2036) 2012

(2010 - 2013) 2130

(2053 - 2315) 2183

(2180 - 2186) 2132

(2132 - 2132) 2132

(2128 - 2136)

1,1,1,3-C13Cl4 (2) 1934

(1913 - 1935) 1908

(1908 - 1908) 1932

(1932 - 1932) 1934

(1934 - 1934) 2036

(1955 - 2036) 2106

(2106 - 2106) 2072

(2072 - 2072) 2122

(2122 - 2122) 2238

(2220 - 2239) 2319

(2319 - 2319) 2237

(2208 - 2240) 2232

(2232 - 2232)

1,1,1,3-C14Cl4 (2) 2042

(2042 - 2042) 2029

(2025 - 2032) 2038

(1941 - 2111) 2051

(2048 - 2053) 2162

(1966 - 2264) 2245

(2242 - 2248) 2183

(1979 - 2291) 2266

(2263 - 2269) N.A.

2468 (2464 - 2472)

N.A. 2333

(2330 - 2337)

1,2,9,10-C10Cl4 2) 1853

(1802 - 1855) 1890

(1887 - 1893) 1876

(1876 - 1876) 1894

(1893 - 1896) 2132

(2065 - 2132) 2105

(2101 - 2109) 2167

(2167 - 2167) 2141

(2138 - 2145) 2590

(2314 - 2601) 2500

(2492 - 2509) 2617

(2507 - 2621) 2558

(2542 - 2574)

Table S4. (Continued) Compounds SPB-octyl HP5 DB17 Inert17 DB225 WAX Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI Measured RI Predicted RI

1,2,10,11-C11Cl4 (2) 1965

(1918 - 1987) 2014

(2007 - 2020) 1985

(1931 - 2158) 2008

(2002 - 2014) 2247

(2177 - 2283) 2248

(2240 - 2257) 2277

(2277 - 2277) 2291

(2282 - 2299) 2708

(2615 - 2787) 2624

(2614 - 2634) 2724

(2620 - 2785) 2664

(2653 - 2675)

1,2,13,14-C14Cl4(2) 2296

(2296 - 2296) 2282

(2278 - 2286) 2312

(2309 - 2485) 2304

(2300 - 2308) 2578

(2578 - 2809) 2551

(2546 - 2557) 2645

(2388 - 2857) 2590

(2583 - 2597) N.A.

2921 (2907 - 2935)

N.A. 2883

(2874 - 2891)

2,5,6,9-C10Cl4 (6) 1740

(1734 - 1745) 1748

(1639 - 1820) 1782

(1769 - 1787) 1754

(1645 - 1825) 2022

(2014 - 2031) 1958

(1839 - 2035) 2053

(2043 - 2059) 1992

(1874 - 2068) 2495

(2437 - 2511) 2343

(2196 - 2456) 2467

(2421 - 2482) 2421

(2306 - 2537)

4,5,7,8-C11Cl4 (6) 1757

(1738 - 1761) 1741

(1678 - 1778) 1774

(1749 - 1782) 1751

(1698 - 1787) 1934

(1908 - 1954) 1931

(1869 - 1969) 1970

(1962 - 1981) 1955

(1895 - 1992) 2272

(2212 - 2290) 2197

(2117 - 2251) 2231

(2165 - 2256) 2250

(2187 - 2291)

1,2,5,6,9,10-C10Cl6 (6) 2199

(2199 - 2200) 2274

(2229 - 2300) 2231

(2229 - 2231) 2243

(2196 - 2282) 2605

(2598 - 2605) 2560

(2501 - 2594) 2659

(2659 - 2659) 2597

(2532 - 2640) 3314

(3314 - 3314) 3140

(3053 - 3185) 3312

(3311 - 3313) 3267

(3167 - 3322)

2,3,4,5,6,7,8,9-C10Cl8 (72) 2181

(2177 - 2199) 2153

(2031 - 2307) 2201

(2199 - 2213) 2171

(2041 - 2335) 2461

(2461 - 2461) 2419

(2263 - 2610) 2525

(2525 - 2525) 2480

(2293 - 2692) 2773

(2769 - 2817) 2851

(2587 - 3127) 2756

(2754 - 2770) 2956

(2622 - 3300)

1,2,3,4,5,6-C11Cl6 (16) 2088

(2030 - 2114) 2006

(1936 - 2109) 2101

(1918 - 2253) 2040

(1961 - 2104) 2366

(2245 - 2391) 2254

(2150 - 2348) 2391

(2339 - 2431) 2308

(2181 - 2389) 2734

(2587 - 2842) 2609

(2454 - 2695) 2639

(2500 - 2733) 2665

(2447 - 2780)

2,3,4,5-C10Cl4 (6) 1656

(1612 - 1677) 1654

(1539 - 1704) 1667

(1619 - 1692) 1662

(1557 - 1699) 1841

(1750 - 1856) 1820

(1680 - 1878) 1844

(1773 - 1884) 1841

(1694 - 1893) 2075

(1915 - 2162) 2042

(1847 - 2119) 2074

(1925 - 2148) 2092

(1819 - 2203)

2,3,4,5-C12Cl4 (6) 1868

(1827 - 1890) 1842

(1757 - 1891) 1875

(1831 - 1900) 1868

(1783 - 1905) 2060

(1962 - 2060) 2041

(1930 - 2103) 2055

(1987 - 2095) 2062

(1946 - 2121) 2283

(2142 - 2387) 2298

(2089 - 2401) 2276

(2141 - 2355) 2292

(2054 - 2418)

1,5,5,6,6,10-C10Cl6 (1) 2190

(2190 - 2190) 2226

(2226 - 2226) 2214

(2214 - 2214) 2209

(2209 - 2209) 2566

(2566 - 2566) 2489

(2489 - 2489) 2619

(2619 - 2619) 2544

(2544 - 2544) 3065

(3065 - 3065) 2965

(2965 - 2965) N.A.

2998 (2998 - 2998)

FIGURES

Figure S1. Chromatograms of several CP standards on the SPB-Octyl column (A,B,D,E) and the SolGel-WAX column (C,F).

Figure S2. RI values against carbon chain length for n-alcohols, n-alkylmethyl esters and 4 groups of CPs

with different chlorination patterns.

Figure S3. Solute descriptors for a selection of CPs calculated using measured RI values from all columns

in this study (including both DB-225ms and SolGel-WAX). Error bars indicate the standard errors from

multiple linear regression analysis.

1,1,

1,3-

C 10Cl 4

2,3,

4,5-

C 10Cl 4

4,5,

7,8-

C 11Cl 4

2,5,

6,9-

C 10Cl 4

1,2,

9,10

-C10Cl 4

1,2,

3,4,

5,6-

C 11Cl 6

2,3,

4,5,

6,7,

8,9-

C 10Cl 8

1,1,

1,3,

9,10

-C10Cl 6

1,2,

5,6,

9,10

-C10Cl 6

-0.5

0.0

0.5

1.0

1.5

2.0

7

8

9

10

11

Des

cri

pto

r v

alu

e (

E,

A a

nd

S

)D

es

crip

tor v

alu

e (L

)

E descriptor

A descriptor

L descriptor

S descriptor

Figure S4. Predicted RI values from COSMO-RS vs measured RI values for all compounds. The vertical

and horizontal error bars show the range of measured RIs for multiple peaks.

Figure S5. Predicted RI values with corrections vs measured RI values for CPs. The vertical and horizontal

error bars show the range of measured RIs for multiple peaks.

Figure S6. Calculated log Kair/polymer partition coefficients from COSMOthermX versus the elution

temperature. Panel A shows how the elution temperatures obtained from the retention time and the

applied GC temperature program were used to derive the partition coefficient for the reference

compounds. Panel B shows how the average Kair/polymer partition coefficient is used to back-calculate the

elution temperature for each compound.

Figure S7a. Mass spectra of (A) 1,1,1,3-C10Cl4, (B) 2,5,6,9-C10Cl4, (C) 1,2,9,10-C10Cl4, and (D) 1,1,1,3,9,10-

C10Cl6 obtained by GC-APCI-TOF-MS analysis.

m/z

m/z

m/z

m/z

[M-Cl]+

[M-2H-2Cl]+

[M-2H-3Cl]+

[M-H-Cl]+[M-2H-2Cl]+

[M-2H-3Cl]+

[M-Cl]+

[M-2H-2Cl]+[M-2H-3Cl]+

[M+H3O]+

[M-H-Cl]+[M-H-2Cl]+

[M-2H-3Cl]+

[M-3H-4Cl]+

A

B

C

D

Figure S7b. Mass spectra of (E) 1,2,5,6,9,10-C10Cl6, (F) 1,5,5,6,6,10-C10Cl6, (G) 1,1,1,3,8,10,10,10-C10Cl8,

and (H) 2,3,4,5,6,7,8,9-C10Cl8 obtained by GC-APCI-TOF-MS analysis.

m/z

m/z

m/z

m/z

[M-H-Cl]+

[M-H-2Cl]+[M-2H-3Cl]+

[M-H-Cl]+

[M-H-2Cl]+

[M-2H-3Cl]+

[M-3H-4Cl]+

[M-H-Cl]+[M-2H-2Cl]+

[M-2H-3Cl]+

[M-3H-4Cl]+

[M-H-Cl]+

[M-H-2Cl]+

[M-2H-3Cl]+

E

F

G

H

Figure S8. Relationship between abundances of CP isomer peaks and values of (A) fragmentor voltage,

(B) capillary voltage, (C) corona current, and (D) gas temperature of APCI-TOF-MS system.

0

2000

4000

6000

8000

10000A

bu

nd

ance

Fragmentor (V)

A

0

2000

4000

6000

8000

10000

Ab

un

dan

ce

Capillary voltage (V)

B

0

2000

4000

6000

8000

10000

12000

Ab

un

dan

ce

Corona current (μA)

C

0

2000

4000

6000

8000

10000

12000

14000

16000

Ab

un

dan

ce

Gas temperature (°C)

D

1,1,1,3-C10Cl4

2,5,6,9-C10Cl4

1,2,9,10-C10Cl4

1,1,1,3,9,10-C10Cl6

1,2,5,6,9,10-C10Cl6

1,5,5,6,6,10-C10Cl6

1,1,1,3,8,10,10,10-C10Cl8

Reference

1. Curvers, J., Rijks, J., Cramers, C., Knauss, K. & Larson, P. Temperature programmed retention indices:

Calculation from isothermal data. Part 1: Theory. J. High Resolut. Chromatogr. 8, 607–610 (1985).

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